HCSGD entry for TERT


1. General information

Official gene symbolTERT
Entrez ID7015
Gene full nametelomerase reverse transcriptase
Other gene symbolsCMM9 DKCA2 DKCB4 EST2 PFBMFT1 TCS1 TP2 TRT hEST2 hTRT
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0000723Telomere maintenanceTASbiological_process
GO:0000781Chromosome, telomeric regionICcellular_component
GO:0000783Nuclear telomere cap complexICcellular_component
GO:0003720Telomerase activityIDAmolecular_function
GO:0003721Telomeric template RNA reverse transcriptase activityIDA TASmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005654NucleoplasmIDA TAScellular_component
GO:0005697Telomerase holoenzyme complexIDAcellular_component
GO:0005730NucleolusIEAcellular_component
GO:0005737CytoplasmIEAcellular_component
GO:0007004Telomere maintenance via telomeraseIMP TASbiological_process
GO:0016605PML bodyIDAcellular_component
GO:0022616DNA strand elongationIDAbiological_process
GO:0032203Telomere formation via telomeraseIDAbiological_process
GO:0042162Telomeric DNA bindingTASmolecular_function
GO:0042803Protein homodimerization activityIDAmolecular_function
GO:0046872Metal ion bindingIEAmolecular_function
GO:0070034Telomeric RNA bindingIDAmolecular_function
GO:0090399Replicative senescenceIMPbiological_process
GO:2001240Negative regulation of extrinsic apoptotic signaling pathway in absence of ligandIMPbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.75414958400.08881923180.99999024730.5652347679

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Down-0.0531582552
GSE13712_SHEARUp0.1187663310
GSE13712_STATICUp0.0934580877
GSE19018Up0.1744409900
GSE19899_A1Up0.1090138039
GSE19899_A2Up0.1604990652
PubMed_21979375_A1Down-0.0783524508
PubMed_21979375_A2Up0.0973716968
GSE35957Up0.1077267131
GSE36640Down-0.0000452232
GSE54402Down-0.0642637060
GSE9593Up0.0511964751
GSE43922Up0.0741276647
GSE24585Up0.0310176400
GSE37065Down-0.0120810557
GSE28863_A1Down-0.0342884429
GSE28863_A2Up0.1683865673
GSE28863_A3Down-1.1357217450
GSE28863_A4Down-1.6904722897
GSE48662Down-0.0057092559

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Name

Drug

Accession number

ZidovudineDB00495 APRD00449
GV1001DB04937 -
Grn163lDB05036 -

  • MicroRNAs

  • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-138-5pMIMAT0000430MIRT003991Luciferase reporter assay//Reporter assay;OtherFunctional MTI18201269
hsa-miR-498MIMAT0002824MIRT006931Luciferase reporter assayFunctional MTI23055531
hsa-miR-193b-3pMIMAT0002819MIRT016371MicroarrayFunctional MTI (Weak)20304954
hsa-miR-335-5pMIMAT0000765MIRT017613MicroarrayFunctional MTI (Weak)18185580
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  • mirRecord
No target information from mirRecord

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 263 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

27311997Involvement of the NFX1-repressor complex in PKC-delta-induced repression of hTERT transcription
27311997The human telomerase reverse transcriptase (hTERT) gene encodes an enzyme responsible for maintaining the integrity of chromosomal ends
27311997Previously, we reported that hTERT repression is required for the induction of cellular senescence
27311997Thus, transcriptional regulation mechanisms of the hTERT gene may be related to the mechanisms of cellular senescence
27311997In the present study, we clarified the molecular mechanism of hTERT repression by protein kinase C (PKC)-delta, one of the cellular senescence-inducing factors
27311997The results showed that a repressor complex composed of NFX1-91, mSin3A and histone deacetylase 1 was involved in the PKC-delta-induced repression of the hTERT promoter, which resulted in the repression of hTERT transcription
27311997These results suggest that targeted recruitment of the NFX1-91 complex to the hTERT promoter is a potential mechanism for repressing hTERT transcription and further inducing cellular senescence
27357325The transcriptional activation of human telomerase reverse transcriptase (hTERT) is critical for telomerase expression
27357325Although several transcriptional activators have been identified, factors responsible for enhancing the hTERT promoter remain to be fully elucidated
27357325Changes in telomerase activity using telomere repeat amplification protocol assay were assessed, and the gene expression levels of hTERT were then examined
27357325This increase was consistent with increases in the protein and mRNA expression levels of hTERT
27357325In luciferase assays, the hTERT promoter was activated by GLTSCR2
27352265The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene
27352265The TERT gene is involved in DNA protection, cellular aging processes, and cancer
27339908In senescent ADhMSCs, 4-MU also counteracted the REAC ability to rescue the gene expression of TERT, and the associated resumption of telomerase activity
27297181Transgenic expression of Telomerase reverse transcriptase (Tert) improves cell proliferation of primary cells and enhances reprogramming efficiency into the induced pluripotent stem cell
27297181We generated a conditional transgenic mouse line, carrying the telomerase reverse transcriptase (Tert) expression cassette, controlled by the Cre-loxP-mediated recombination
27297181In our study, Cre recombinase expression efficiently activated Tert expression, resulting in its increased enzymatic activity, which extended the period of cellular proliferation until the keratinocytes entered senescence
27297181This suggests that transgenic Tert expression is effective in enhancing primary cell proliferation
27297181Notably, Tert expression increased colony formation of induced pluripotent stem (iPS) cells after the introduction of four reprogramming factors, Oct-4, klf4, SOX-2, and c-Myc into the transgenic fibroblasts
27297181To the best of our knowledge, this is the first study to show that the transgenic Tert expression enhances reprogramming efficiency of iPS cells, which indicates a critical role for Tert in the reprogramming process
27221886Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation
27221886PGC-1alpha expression was repressed after carbion-ion irradiation, and hTERT inhibition by MST-312 could further exacerbate this effect
27142689GRIM-19 Restores Cervical Cancer Cell Senescence by Repressing hTERT Transcription
27142689The HR-HPV E6 can activate hTERT promoter by interacting with E6AP or other binding proteins and by stabilizing the interaction between hTERT and E6AP
27142689We also found that GRIM-19 expression in cervical cancer cells could inhibit telomerase activity by inhibiting the transactivation of the hTERT promoter by E6, thereby promoting cervical cancer cell senescence
27142689Moreover, we identified a negative correlation between GRIM-19 and hTERT expression in cervical cancer tissues
27142689Suppression of GRIM-19 and induction of hTERT levels were associated with lymph node metastasis, advanced clinical stage, and poor prognosis
27103453Telomerase is composed of the catalytic subunit TERT (Telomerase reverse transcriptase),RNA subunit TERC (Telomerase RNA component) and other telomerase associated proteins
27103453Trafficking and assemble of TERT and TERC, as well as recruitment to telomeres, are also involved in this process
26952515The aim of the present study was to investigate Ki-67, TPX2, TOP2A and hTERT mRNA expression levels in specimens from patients with GISTs to define relationships between proliferation activity and biological potential and progression of the disease
26952515We measured Ki-67, TPX2, TOP2A and hTERT mRNA levels using quantitative real-time reverse transcription PCR (RQ RT PCR)
26952515The highest Ki-67, TPX2, TOP2A and hTERT mRNA expression levels were found in the highly proliferative BLs (18 specimens), in comparison with GISTs (137 specimens) and LMSs (9 specimens)
26952515We observed association between higher Ki-67, TPX2 and hTERT mRNA levels and the GISTs with malignant potential
26952515Univariate analysis (57 patients with available follow-up information) of survival (Kaplan Meier curves method) revealed a correlation between higher levels of TPX2, Ki-67 and hTERT markers and shorter event-free survival (EFS) or poorer overall survival (OS)
26952515Proliferation markers of Ki-67, TPX2, TOP2A and hTERT are suitable markers for detection the proliferation activity and telomerase activity of these tumors
26952515Furthermore, the assessment of TPX2, Ki-67 and hTERT expression levels is appropriate for determination of malignant potential of GISTs
26637971Expression of SIRT1 and telomerase reverse transcriptase (TERT) was downregulated in old SkMs, and transduction of old SkMs with lentiviral miR-195 inhibitor significantly restored their expression
26571381GSE4 expression also activated c-myc and TERT promoters and increase of c-myc, TERT and TERC expression
26571381Mutation of the Aspartic Acid residue that is conserved in the pseudouridine synthase domain present in GSE4 did not impair its activity, except for the repression of c-myc promoter activity and the decrease of c-myc, TERT and TERC gene expression in dyskerin-mutated cells
26546739A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition
26546739The TERT gene encodes for the reverse transcriptase activity of the telomerase complex and mutations in TERT can lead to dysfunctional telomerase activity resulting in diseases such as dyskeratosis congenita (DKC)
26546739Here, we describe a novel TERT mutation at position T1129P leading to DKC with progressive bone marrow (BM) failure in homozygous members of a consanguineous family
26518879Mutations of human telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) are associated with a subset of lung aging diseases, but the mechanisms by which TERC and TERT participate in lung diseases remain unclear
26518879In this report, we show that knock-out (KO) of the mouse gene Terc or Tert causes pulmonary alveolar stem cell replicative senescence, epithelial impairment, formation of alveolar sacs, and characteristic inflammatory phenotype
26487427It has been shown before that the combination of human CDK4R24C, cyclin D, and TERT induces the efficient cellular immortalization of cells derived from humans, bovine, swine, and monkeys
26418880Suppressor of Ty homolog-5, a novel tumor-specific human telomerase reverse transcriptase promoter-binding protein and activator in colon cancer cells
26418880The human telomerase reverse transcriptase (hTERT) promoter promotes differential hTERT gene expression in tumor cells and normal cells
26418880However, information on the mechanisms underlying the differential hTERT transcription and induction of telomerase activity in tumor cells is limited
26418880In the present study, suppressor of Ty homolog-5 (SPT5), a protein encoded by the SUPT5H gene, was identified as a novel tumor-specific hTERT promoter-binding protein and activator in colon cancer cells
26418880We verified the tumor-specific binding activity of SPT5 to the hTERT promoter in vitro and in vivo and detected high expression levels of SUPT5H in colorectal cancer cell lines and primary human colorectal cancer tissues
26418880Inhibition of endogenous SUPT5H expression by SUPT5H gene-specific short hairpin RNAs effectively attenuated hTERT promoter-driven green fluorescent protein (GFP) expression, whereas no detectable effects on CMV promoter-driven GFP expression in the same cells were observed
26418880Our results demonstrated that SPT5 contributes to the up-regulation of hTERT expression and tumor development, and SUPT5H may potentially be used as a novel tumor biomarker and/or cancer therapeutic target
26414604Telomerase Reverse Transcriptase and Peroxisome Proliferator-Activated Receptor gamma Co-Activator-1alpha Cooperate to Protect Cells from DNA Damage and Mitochondrial Dysfunction in Vascular Senescence
26414604Telomerase reverse transcriptase (TERT), the protein subunit of telomerase, is expressed only transiently in a subset of adult somatic cells, which include stem cells and smooth muscle cells
26414604A recent report from Xiong and colleagues demonstrates a pivotal role for the transcription co-factor peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) in maintaining TERT expression and preventing vascular senescence and atherosclerosis in mice
26414604Ablation of PGC-1alpha reduced TERT expression and increased DNA damage and reactive oxygen species (ROS), resulting in shortened telomeres and vascular senescence
26414604In the ApoE(-/-) mouse model of atherosclerosis, forced expression of PGC-1alpha increased expression of TERT, extended telomeres, and reversed genomic DNA damage, vascular senescence, and the development of atherosclerotic plaques
26414604Alpha lipoic acid (ALA) stimulated expression of PGC-1alpha and TERT and reversed DNA damage, vascular senescence, and atherosclerosis, similarly to ectopic expression of PGC-1alpha
26414604The possibility that ALA might induce TERT to extend telomeres in human cells suggests that ALA may be useful in treating atherosclerosis and other aging-related diseases
26414604However, further investigation is needed to identify whether ALA induces TERT in human cells, which cell types are susceptible, and whether such changes have clinical significance
26390028Of these miRNAs, we found miR-195 directly targeted 3'-untranslated region of Tert gene by computational target prediction analysis and luciferase assay, and knockdown of miR-195 significantly increased Tert expression in OMSCs
26390028Moreover, silencing miR-195 in OMSCs by transfection of miR-195 inhibitor significantly restored antiaging factors expression including Tert and Sirt1 as well as phosphorylation of Akt and FOXO1
26299964PGC-1alpha deletion reduces expression and activity of telomerase reverse transcriptase (TERT) and increases p53 levels
26299964Ectopic expression of PGC-1alpha coactivates TERT transcription and reverses telomere malfunction and DNA damage
26299964Furthermore, alpha lipoic acid (ALA), a non-dispensable mitochondrial cofactor, upregulates PGC-1alpha-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE) signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy
26230157Serum Senescence by Directly Interacting with Human Telomerase Reverse Transcriptase
26230157Senescence was measured at different cellular stages by senescence-associated beta-galactosidase (SA-beta-gal) activity, human telomerase reverse transcriptase (hTERT) activity, p21 protein levels, and ROS production
26230157HUVECs over-expressing full-length SGK1 (wild-type SGK1 [SGK1WT]) showed a decrease in SA-beta-gal and p21 expression and a corresponding increase in hTERT activity in the early stages of aging
26230157A direct interaction between SGK1WT and hTERT was also shown by co-immunoprecipitation
26230157The SGK1Delta60 isoform, lacking the amino-terminal 60 amino acids, did not show interaction with hTERT, suggesting a pivotal role of this protein site for the SGK1 anti-aging function
26201603Sequence variation in telomerase reverse transcriptase (TERT) as a determinant of risk of cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study
26201603BACKGROUND: Telomerase reverse transcriptase (TERT) maintains telomere ends during DNA replication by catalyzing the addition of short telomere repeats
26201603The aim of the present study was to determine whether six variants in the TERT gene are associated with risk of incident coronary heart disease, incident ischemic stroke, and mortality in participants in the biracial population-based Atherosclerosis Risk in Communities (ARIC) study, including rs2736100 that was found to influence mean telomere length in a genome-wide analysis
26201603Haplotype tagging SNPs in TERT were genotyped using a custom array containing nearly 49,000 SNPs in 2,100 genes associated with cardiovascular and metabolic phenotypes
26201603Cox proportional hazards models were used to assess the association between the TERT polymorphisms and incident cardiovascular disease and mortality over a 20-year follow-up period in 8,907 whites and 3,022 African-Americans with no history of disease at the baseline examination, while individuals with prevalent cardiovascular disease were not excluded from the analyses of mortality
26196672Immortalisation with hTERT Impacts on Sulphated Glycosaminoglycan Secretion and Immunophenotype in a Variable and Cell Specific Manner
26196672Immortalisation via the reintroduction of the catalytic component of telomerase, hTERT, could allow repeated, longitudinal studies to be performed while bypassing senescent phenotypes
26196672METHODS: Three human cell types: bone marrow-derived stromal cells (BMA13), embryonic stem cell-derived (1C6) and chondrocytes (OK3) were transduced with hTERT (BMA13H, 1C6H and OK3H) and proliferation, surface marker expression and tri-lineage differentiation capacity determined
26196672RESULTS: hTERT expression was confirmed in transduced cells with proliferation enhancement in 1C6H and OK3H cells but not BMA13H
261966721C6 and BMA13 demonstrated osteogenic and adipogenic differentiation but mineralised matrix and lipid accumulation appeared reduced post hTERT transduction
26196672CONCLUSION: In conclusion, hTERT transduction could, but did not always, prevent senescence and cell phenotype, including differentiation potential, was affected in a variable manner
26084784Along with telomerase activity, telomere repeats and an attempt on identification of telomerase reverse transcriptase (PmTERT) were made
26084784PmTERT protein sequence (partial) shared 100 % identity with the TERT sequence of Daphnia pulex, 27 % sequence identity with Purple sea urchin and 24-25 % with Zebra fish
26082434Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation
26082434The catalytic subunit, human telomerase reverse transcriptase (hTERT), is stabilized by phosphorylation
26082434Docking predictions and mutational analyses revealed that binding occurred between a hydroxyl group (C'3-OH) in S1P and Asp(684) in hTERT
26082434Thus, our data suggest that S1P binding to hTERT allosterically mimicks phosphorylation, promoting telomerase stability and hence telomere maintenance, cell proliferation, and tumor growth
26034007Telomerase contains a catalytic subunit, the telomerase reverse transcriptase (hTERT)
26034007Introduction of TERT into human cells extends both their lifespan and their telomeres to lengths typical of young cells
26034007The regulation of TERT involves transcriptional and posttranscriptional molecular biology mechanisms
26034007ROS-mediated oxidative stress induces the depletion of hTERT from the nucleus via export through the nuclear pores
26034007Nuclear export is initiated by ROS-induced phosphorylation of tyrosine 707 within hTERT by the Src kinase family
25952632Under these conditions, the anti-senescence genes TERT, bFGF, VEGF, and ANG were increased, whereas the senescence-related genes ATM, p21, and p53 were decreased
25952632We have shown that RG108 significantly induces the expression of TERT by blocking methylation at the TERT promoter region
25873431Acidified bile acids increase hTERT expression via c-myc activation in human gastric cancer cells
25873431Human telomerase reverse transcriptase (hTERT) is upregulated in most cancer cell types as well in immortalized cells
25873431We report here that bile acids under acidified media increase hTERT expression via c-myc activation in primary human gastric cancer cell lines
25873431Importantly, pharmacologic inhibition of c-myc using 10058-F4 prevented hTERT induction by DCA or CDCA in gastric cancer cells under acidic conditions
25873431Bile acids (DCA and CDCA) under acidic conditions increased hTERT expression in human gastric cancer cells by activation of c-myc transcription
25845638The expression of related proteins, including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western blot
25845638The immunoblotting confirmed that ASP attenuated inhibition of phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased the expression of gp91-phox
25760322Aging is associated with telomere shortening, and both telomerase reverse transcriptase (TerT) and RNA (TerC) are essential to maintain telomere length
25760322To define a role of telomerase deficiency in susceptibility to AKI, we used ischemia/reperfusion injury in wild-type mice or mice with either TerC or TerT deletion
25760322However, either TerC or TerT knockout significantly delayed recovery compared with wild-type mice
25760322Electron microscopy showed increased autophagosome formation in renal tubular epithelial cells in wild-type mice but a significant delay of their development in TerC and TerT knockout mice
25719742The growth inhibition was correlated with down-regulation of the catalytic subunit of telomerase (hTERT) gene (p < 0
25686834We discovered that miR-34a potently targeted c-Myc and FoxM1, both of which were involved in the activation of telomerase reverse transcriptase (hTERT) transcription, essential for the sustaining activity of telomerase to avoid senescence
25684230In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss
25662949Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats
25574106Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations
25574106We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR
25574106Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference
25574106Considering the geographic origins of HCC tumors tested, TERT promoter mutation frequencies were higher in African (53%), when compared to non-African (24%) tumors (P = 0
25574106There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism (P = 0
25574106CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer, and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control
25572145Re-expression of E2 expression with TNF-alpha treatment resulted in an increase in the expression of anti-apoptotic Bcl2 (B-cell lymphoma 2) protein and other pro-survival genes like cyclin D1 (cyc D1), survivin and hTERT (human telomerase reverse transcriptase)
25565635Expression of TERT was always negative
25516136RESULTS: C allele of TERT polymorphism was more prevalent among hypertensive patients (OR: 3
25364077Senescence markers showed reduced TERT and cyclin A and increased p16INK4a expression, with higher IL-6 plasma levels in SF-exposed mice
25360110Interestingly, markers indicating cellular senescence or oxidative stress (SNCA, CASP3, CAT, SOD2, and TERT) were largely unchanged within the ENS
25359865Homocysteine accelerates senescence of endothelial cells via DNA hypomethylation of human telomerase reverse transcriptase
25359865Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity
25359865Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay
25359865Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels
25305686The finding here might lead to a new class of telomerase activators that act directly or indirectly on telomerase, rather than through the reactivation of the telomerase reverse transcriptase (TERT) gene associated with other telomerase activators found in the literature
25279549High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells
25279549The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells
25279549BORIS silencing strongly down-regulated the expression of hTERT, stem cell and cancer stem cell marker genes
25244922Telomeres need to be replicated in each cell cycle and protected from DNA-processing enzymes, tasks that cells execute using specialized protein complexes such as telomerase (that includes TERT), which aids in telomere maintenance and replication, and the shelterin complex, which protects chromosome ends
25224681Transcription of the catalytic telomerase subunit (TERT) was also increased in REAC-treated cells at all passages
25187009In this study, we established nonhuman primate primary cell lines by introducing the genes for CDK4R24C, cyclin D1, and hTERT
25187009The present study shows that introduction of the CDK4R24C, cyclin D1, and hTERT genes are effective methods of establishing nonhuman primate cell lines
25142166However, of the components of telomerase, telomerase reverse transcriptase was up-regulated along temperature elevation
25078983The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot
25078983LY294002 pre-treatment significantly alleviated Ang II-induced HUVEC senescence, and partly reversed the elevation of TERT, UCP2, p-Akt, c-myc and p53 protein levels
25042573Specifically, we address how p53 and telomerase reverse transcriptase (TERT) activity switch their roles from cytoprotective to detrimental and also examine the role of microRNAs in cell aging
25038529These findings were reversible after transduction of presenescent cultures with telomerase reverse transcriptase, enabling late-passage cultures to escape senescence
25032857In this study, we show that the endogenous expression levels of Zfp637 and mouse telomerase reverse transcriptase (mTERT) are downregulated during oxidative stress-induced premature senescence and in senescent tissues from naturally aged mice
25032857The overexpression of Zfp637 markedly increases mTERT expression and telomerase activity, maintains telomere length, and inhibits both H2O2 and D-galactose-induced senescence accompanied by a reduction in the production of reactive oxygen species (ROS)
25032857In contrast, the knockdown of Zfp637 significantly aggravates cellular senescence by downregulating mTERT and telomerase activity, accelerating telomere shortening, and increasing ROS accumulation
25032857In addition, the protective effect of Zfp637 against premature senescence is abrogated in the absence of mTERT
25032857We further confirm that Zfp637 binds to and transactivates the mTERT promoter (-535/-502) specifically
25012820We have reported previously that the DNA-PKcs (DNA-dependent protein kinase catalytic subunit)-interacting protein KIP associates with telomerase through an interaction with hTERT (human telomerase reverse transcriptase)
25000517FOXO3a potentiates hTERT gene expression by activating c-MYC and extends the replicative life-span of human fibroblast
25000517In our previous studies, we reported that SIRT1 prevents cellular senescence in human fibroblast, and that SIRT1-induced inhibition of cellular senescence is due to enhanced hTERT gene expression
25000517In this study, we investigate the molecular mechanisms behind SIRT1-induced potentiation of hTERT transcription and show that FOXO3a functions downstream of SIRT1 and prevents the induction of cellular senescence by enhancing hTERT gene expression
25000517Furthermore, we found that FOXO3a-induced potentiation of hTERT gene expression is regulated in a c-MYC/E-box dependent manner
25000517The resulting increase in c-MYC leads to higher levels of c-MYC recruited to the hTERT promoter and, in turn, activates hTERT gene expression
24970747Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells
24970747Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex
24970747By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan
24970747Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration
24970747We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells
24970747Inhibition of TERT expression or activity by using siRNA (100nM) or specific inhibitors (100nM) reduced basal 2-deoxyglucose uptake by ~50%, in all cell types, without altering insulin responsiveness
24970747In contrast, TERT over-expression increased glucose uptake by 3
24970747In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane
24970747Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells
249703855-aza-2'-deoxycytidine-mediated c-myc Down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia
24934763We further noted that expression of p53 blocks the neuronal conversion, whereas expression of human telomerase reverse transcriptase (hTERT) induces it
24920674On the basis of these results, we presumed a link between hTERT repression and the induction of cellular senescence
24917814SIRT1 protected MSCs from age-related DNA damage, induced telomerase reverse transcriptase (TERT) expression and enhanced telomerase activity but did not affect telomere length
24816985Changes in PTTG1 by human TERT gene expression modulate the self-renewal of placenta-derived mesenchymal stem cells
24816985The human TERT gene enhances the self-renewal of MSCs, but the mechanism of self-renewal and the interactions among TERT-gene-related molecules remain unknown
24816985The objectives of this study were to generate immortalized MSCs derived from MSCs isolated from placenta (naive) by human TERT gene transfection with the AMAXA gene delivery system, to compare their characteristics, and to investigate whether increased TERT expression affected the pituitary tumor transforming gene (PTTG1; also known as securin), which is involved in chromosome segregation during mitosis
24816985TERT-immortalized cells (TERT+) with a prolonged life span displayed high PTTG1 expression
24816985Moreover, TERT bound to PTTG1 formed complexes with chaperones such as Ku70 and heat shock protein 90
24816985Thus, placental MSCs immortalized by TERT gene transfection display differentiation potential and exhibit enhanced self-renewal through a balanced interaction of PTTG1 and chaperones
24816985The interaction between TERT and PTTG1 by association of Ku70 might be important for the enhancement of the limited self-renewal activity of MSCs and for understanding the regulatory mechanisms of self-renewal
24713059We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT
24713059The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex
24713059Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres
24713059The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid
24713059The network of interaction of hTERT transcripts has been further analyzed following the competing endogenous (ce) RNA hypotheses (messenger [m] RNAs cross-talk via micro [mi] RNAs) using the miRWalk database and tools (www
24599132This review summarizes recent insights to the noncanonical functions of telomerase reverse transcriptase (TERT) catalytic subunit, in particular in cancer progression, and highlights two major signaling mechanisms involved in the cross-talk with TERT-the NF-kappaB and Wnt/beta-catenin pathways
24599132We propose a feed-forward regulatory loop mechanism underlying TERT activation in cancers in which TERT acts as a transcriptional modulator of oncogenic signaling pathways that sustain its own levels and control the induction of target genes critical for tumor cell survival and proliferation
24599132Finally, we provide a new perspective on telomerase-targeted cancer therapies and suggest possible interventions targeting the nontelomeric roles of TERT
24589663To overcome limitations in cell-line establishment, we attempted to immortalize bovine and porcine fibroblasts by transduction of multiple cell cycle regulators (mutant cyclin dependent kinase 4, cyclin D and telomerase reverse transcriptase)
24572088This critical step is successfully accomplished by EBV through TERT expression and telomerase activation in infected cells
24572088We herein review the complex interplay between EBV and TERT/telomerase in EBV-driven tumorigenesis
24572088In this respect, our recent finding that TERT inhibition sensitizes EBV+ lymphoma cells to antivirals through activation of EBV lytic replication is particularly promising and provides a rationale for the activation of clinical studies aimed at assessing the effects of combination therapies with TERT inhibitors and antivirals for the treatment of EBV-associated malignancies
24508601In addition to new structures of TERT and TER domains, the first structures of telomerase protein domains beyond TERT, and their complexes with TER or telomeric single-stranded DNA, were reported
24478790Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1
24361335The 58-kda microspherule protein (MSP58) represses human telomerase reverse transcriptase (hTERT) gene expression and cell proliferation by interacting with telomerase transcriptional element-interacting factor (TEIF)
24361335The human telomerase reverse transcriptase (hTERT) gene, which encodes an essential component for telomerase activity that is involved in cellular immortalization and transformation, is strictly regulated at the gene transcription level
24361335Here we identify telomerase transcriptional element-interacting factor (TEIF) as a novel MSP58-interacting protein and determine the effect of MSP58 on hTERT transcription
24361335This study thus provides evidence showing MSP58 to be a negative regulator of hTERT expression and telomerase activity
24361335Additionally, stable overexpression of MSP58 protein in HT1080 and 293T cells decreased both endogenous hTERT expression and telomerase activity
24361335Chromatin immunoprecipitation assays showed that MSP58 binds to the hTERT proximal promoter
24361335Furthermore, overexpression of MSP58 inhibited TEIF-mediated hTERT transactivation, telomerase activation, and cell proliferation promotion
24339974Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro
24336070More recent clinical evidence points to telomere shortening caused by NRTI triphosphate-induced inhibition of telomerase, suggesting telomerase reverse transcriptase (TERT) inhibition as being a pathogenetic contributor to premature aging in HIV/AIDS
24109236HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and together they posttranscriptionally increase hTERT expression, the catalytic subunit of telomerase
24109236NFX1-123 interacts with hTERT mRNA and stabilizes it, leading to greater telomerase activity and the avoidance of cellular senescence
24109236The PAM2 motif and R3H protein domains in NFX1-123, which were important for increased hTERT expression, were also important in the augmentation of Notch1 expression by 16E6
23983186Previous studies have used lipofectamine or recombinant adeno-associated viral (rAAV) vectors to deliver human telomerase reverse transcriptase (hTERT) into ovine or HNP cells to prolong the activity of nucleus pulposus cells with limited success
23983186Here we developed a lentiviral vector bearing both hTERT and a gene encoding green fluorescence protein (L-hTERT/EGFP)
23983186This vector efficiently mediated both hTERT and EGFP into freshly isolated HNP cells
23897841Expression of constitutively activated Stat3 or human telomerase reverse transcriptase (hTERT), as well as knockdown of Shp2f, efficiently counteracted GADD45G-induced senescence
23830072Chlamydia trachomatis inhibits telomeric DNA damage signaling via transient hTERT upregulation
23830072In particular, human telomerase catalytic subunit (hTERT) mRNA expression and catalytic subunit activity were increased in acute infected late passage IMR90E1A cells
23765615DPSCs are isolated from human dental pulp tissues and transfected using hTERT
23765615The results reveal an absence of altered DPSC morphology and phenotype following the exogenous introduction of the hTERT gene, which is coupled with a significant reduction in p16 mRNA expression
23765615This provides insight into how to circumvent in vitro dental pulp stem cell death following the exogenous introduction of hTERT
23718894Furthermore, real-time RT-PCR analysis revealed approximately two-fold reductions in EST2 mRNA but no change in TLC1 RNA in thymol-treated S
23718894EST2 encodes the essential reverse transcriptase subunit of telomerase that uses TLC1 RNA as a template during addition of TG(1-3) repeats to maintain telomere ends
23718894This study provides compelling evidence that a primary mode of thymol antifungal activity is through inhibition of transcription of EST2 and thus telomerase activity
23691139They also reactivate telomerase reverse transcriptase
23612978We found that Vpr inhibited telomerase activity by down-regulating TERT protein, a catalytic subunit of telomerase
23612978As a molecular adaptor, Vpr enhanced the interaction between TERT and the VPRBP substrate receptor of the DYRK2-associated EDD-DDB1-VPRBP E3 ligase complex, resulting in increased ubiquitination of TERT
23597430IL-8 also increased telomerase activity which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT), whereas these effects were significantly attenuated by SB 225002 (selective non-peptide CXCR2 antagonist)
23562826The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy
23562826BACKGROUND: Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence
23562826TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL)
23562826The association of TERT SNPs with longevity remains uncertain and varies with ethnicity
23562826The aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity
23562826CONCLUSIONS: The TERT MNS16A*L allele appears negatively associated with longevity
23516479Using a novel mouse model, we tested the potential of GRN510 to limit fibrosis induced by bleomycin in mTERT heterozygous mice
23515239We sought to reduce the variability of these cells by insertion and expression of human telomerase reverse transcriptase (TERT) to immortalize the cell line
23515239Expression of TERT mRNA and protein activity was confirmed in the TERT-transduced cells
23515239Mock-transduced hMSCs had almost undetectable levels of TERT mRNA and protein activity and lost proliferation potential at PDL 14
23503666Compared to the controls, telomerase activity, the expression of human telomerase reverse transcriptase (hTERT) and c-Myc in the irradiated HUVECs were downregulated during serial passage
23321015G-quadruplex ligands can attenuate telomerase activity by inducing G-quadruplex formation at the 3'-overhang of telomere and at the human telomerase reverse transcriptase (hTERT) promoter; the former prevents telomerase from accessing the telomere, and the latter acts as a transcriptional silencer
23321015The present investigation found that perylene derivatives PM2 and PIPER induced G-quadruplex formation from both telomeric DNA and the hTERT promoter region in vitro
23321015When A549 human lung cancer cells were treated with these compounds, hTERT expression was down-regulated
23268535These four genes encode two surfactant proteins, surfactant protein C (encoded by SFTPC) and surfactant protein A2 (SFTPA2), and two components of the telomerase complex, telomerase reverse transcriptase (TERT) and the RNA component of telomerase (TERC)
23185405We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1), telomere regulation and elongation (TERT), and in the response to biopsychological stress (FOS and DUSP1)
23185405Expression of p16(INK4a) and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a), STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls)
23167636However, both telomeric and extratelomeric aberrations are prevented by hTERT, indicating that even non-telomeric damage descends from the lack of telomerase
23080539Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40-TAg) result in telomere extension, but do not prevent SA-DNAm
22973556The human holoenzyme telomerase is a ribonucleoprotein composed by a catalytic subunit, hTERT, an RNA component, hTR, and a group of associated proteins
22973556The identification of the hTERT as a functional catalytic RT prompted studies of inhibiting telomerase with the HIV RT inhibitor azidothymidine (AZT)
22961627Serine/threonine-protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution
22961627In a search for proteins interacting with human telomerase reverse transcriptase hTERT by the yeast two-hybrid screen using hTERT T-motif as bait, we identified PP2A scaffolding subunit PR65 alpha isoform as an hTERT interacting partner
22961627We showed that both PP2A catalytic subunit PP2AC and scaffolding subunit PR65 interacted with hTERT in vivo and in vitro and inhibited telomerase activity
22961627In addition, we found that PP2A prevented the interaction of hTERT with 14-3-3theta signaling protein, an hTERT binding partner that is required for nuclear localization of hTERT
22961627Activation of PP2A by overexpression of PP2AC or PR65 led to cytoplasmic accumulation of hTERT, which was reversed by treatment with PP2A inhibitor okadaic acid
22841437Telomeres shorten with each successive cell division in normal human cells whereas, in tumors, they are continuously elongated by human telomerase reverse transcriptase (hTERT)
22841437Several strategies of telomerase inhibition are reviewed, including small molecule inhibitors, antisense oligonucleotides, immunotherapies and gene therapies, targeting the hTERT or the ribonucleoprotein subunit hTER
22841437Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001)
22815702OBJECTIVES: Nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV antiretroviral therapy can inhibit human telomerase reverse transcriptase
22661914Heterozygous carriers for mutations in either the telomerase reverse transcriptase (hTERT) or the telomerase RNA template (hTERC) gene displayed striking and comparable telomere length deficits
22652801Notably, ectopic expression of telomerase holoenzyme (hTert) can prevent replicative CS
22633954AUF1 binds and strongly activates the transcription promoter for telomerase catalytic subunit Tert
22569128Furthermore, we demonstrate that oncogenic signalling, frequently associated with initiating cancer growth in humans, dramatically affected telomere structure and function by causing telomeric replication stress, rapid and stochastic telomere attrition, and consequently telomere dysfunction in cells that lack hTERT activity
22554522Combined introduction of Bmi-1 and hTERT immortalizes human adipose tissue-derived stromal cells with low risk of transformation
22554522To this end, combinations of human telomerase reverse transcriptase (hTERT), murine Bmi-1, and SV40 large T antigen (SV40T) were introduced by lentiviral transduction into ASCs
22554522The combination of Bmi-1 and hTERT successfully immortalized human ASCs without significantly perturbing their phenotype or biological behavior
22359661We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations
22353808METHODS AND RESULTS: Purified epithelial cells isolated from ovarian endometriomas using microscopic manipulation were successfully immortalised by combinatorial transfection of human cyclinD1, cdk4 and human telomerase reverse transcriptase (hTERT) genes, whereas the introduction of hTERT alone, or together with cdk4, was insufficient for immortalisation, leading to cellular senescence
22267287Furthermore, genetic variants in and around the TERT gene have been implicated in carcinogenesis
22267287However, several SNPs in the TERT gene, including rs2736122, rs4246742, rs4975605, rs10069690, rs2736100, rs2853676, and rs7726159, were significantly associated with ovarian cancer risk
22267287We observed a significant gene-level association between TERT and ovarian cancer risk (P = 0
22267287CONCLUSION: Our observations suggest that genetic variation in the TERT gene may influence ovarian cancer risk, but the association between average telomere length in PBLs and ovarian cancer remains unclear
22221399Human telomerase reverse transcriptase transfection reduces apoptosis in human penile smooth muscle cells and slows down cellular aging
22221399AIM: To explore effects of human telomerase reverse transcriptase (hTERT) gene transfection on biological behaviors of human penile smooth muscle cells
22221399CONCLUSION: In this study, for the first time, the hTERT gene was transfected into human penile smooth muscle cells, and the gene increased telomerase activity in cells, reduced cell apoptosis, and slowed down cell aging
22197555SIRT1 prevents replicative senescence of normal human umbilical cord fibroblast through potentiating the transcription of human telomerase reverse transcriptase gene
22197555Here, we focused on the human telomerase reverse transcriptase (hTERT) gene as a target of the SIRT1-induced prevention of cellular senescence
22197555Results showed that SIRT1, SIRT1 activator, resveratrol, and SIRT1 activating condition, starved condition, increased the transcription of hTERT in HUC-F2 cells
22197555Next, we found that SIRT1 increased hTERT transcription in a c-MYC-dependent manner, triggered the transcription of the c-MYC gene and increased the amount of c-MYC recruited to the hTERT promoter
22197555Further, SIRT1 increased the transcriptional activation ability of c-MYC and correspondingly increased the amount of acetylated H4 histone at the hTERT promoter
22197555All of these results indicated that SIRT1 activates hTERT transcription through the involvement of c-MYC, and suggested that this SIRT1-induced augmentation of hTERT transcription resulted in the extension of the cellular life span of HUC-F2 cells
22128747The effects of exogenous human telomerase reverse transcriptase expression, p53 knockdown, disruption of the pRb pathway by over-expression of CDK4 and reduced oxygen concentration on the lifespan of primary HCEC were evaluated
22110753However, it has not been elucidated the characteristics of telomere maintenance and progression ability after long-term culture in bladder cancer T24 cells with hTERT dysfunction
22110753METHODOLOGY/PRINCIPAL FINDINGS: In this study, by using a dominant negative mutant human telomerase reverse transcriptase (hTERT) vector to inhibit TA in bladder cancer T24 cells, we observed the appearance of long phenotype of telomere length and the ALT-associated PML body (APB) complex after the 27(th) passage, indicating the occurrence of ALT-like pathway in surviving T24/DN868A cells with telomerase inhibition
22071150Reactivation of telomerase (EST2) expression in the growth-arrested cells led to resumption of cycling and reversal of senescent cell characteristics
22067611RESULTS: With the exogenous expression of hTERT, tDPSCs maintained a continued expression of odontogenic markers for cell proliferation and mineralization (ALP, COL-1, DMP-1, DSPP, OCN amd OPN)as did nDPScs
22067611METHODS: Using a retroviral vector, exogenous human telomerase reverse transcriptase (hTERT) was expressed in tDPSCs
22067611Also examined were the expression of genes involved in proliferation and mineralization such as human alkaline phosphatase (ALP), beta-actin, collagen 1 (col-1), core binding factor (cbfa-1), dentin matrix protein (DMP-1), dentin sialophosphoprotein (DSPP), GAPDH, hTERT, osteocalcin (OCN), osteopontin (OPN) as well as oncoproteins involved in senescence (p16, p21 and p53) using RT-PCR
22067611CONCLUSIONS: These results indicate maintainance of odontoblast-like differentiation characteristics after retroviral transformation with hTERT and suggest a possible link with a reduced p16 expression
21854360In the current review, we have selected nine tumour specific anti-telomerase approaches based on their mechanism of action or the target components of the human telomerase enzyme: Antisense-oligonucleotides, hammerhead ribozymes, dominant negative hTERT, reverse-transcriptase inhibitors, immunotherapy, G-quadruplex stabilisers, gene therapy, small molecule inhibitors and RNA interference
21763315RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer
21763315Human telomerase reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level of gene transcription
21763315Using SILAC-proteomic analysis and molecular studies, we identified the AAA+ ATPase, RuvBl2 as a transcriptional regulator of hTERT and established that this regulation is through cooperation with Ets-2
21763315In colon cancer patients, nuclear expression of RuvBl2 associated with nuclear expression of hTERT, pEts2 and advanced nodal disease (P<0
21763315These data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences
21748355Cloning and characterization of telomerase reverse transcriptase gene in Trichinella spiralis
21748355The telomerase reverse transcriptase (TERT) is primarily known for its ability to elongate telomeres for maintaining chromosomal integrity and delaying cellular senescence
21748355Telomerase includes two core components-an internal RNA moiety acting as a template of DNA extension and a catalytic subunit (TERT) which provides catalytic activity
21748355Here, we described the cloning, sequence, and characterization of the TERT gene from Trichinella spiralis (T
21748355While RT-PCR analysis indicates that TERT mRNA is expressed in T
21708826Neither telomere length nor CRC risk was associated with variation near telomerase reverse transcriptase or other telomere biology genes
21694780We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP
21693539I3C strongly downregulated transcript expression of the catalytic subunit of the human telomerase (hTERT) gene, which correlated with the dose-dependent indole-mediated G(1) cell cycle arrest without altering the transcript levels of the RNA template (hTR) for telomerase elongation
21693539Exogenous expression of hTERT driven by a constitutive promoter prevented the I3C-induced cell cycle arrest and rescued the I3C inhibition of telomerase enzymatic activity and activation of cellular senescence
21693539These results demonstrate that I3C disrupts the combined ERalpha- and Sp1-driven transcription of hTERT gene expression, which plays a significant role in the I3C-induced cell cycle arrest of human breast cancer cells
21647411Interferon alpha on expression of hTERT mRNA in peripheral blood mononuclear cells of patients with chronic hepatitis B
21647411Cell division is closely related to telomerase activity (hTERT mRNA)
21647411Lower expression of lymphocitic hTERT mRNA may easily cause cell aging, which is not beneficial to maintaining a durable lymphocyte division
21647411We quantitatively detected hTERT mRNA from study subjects and made each hTERT mRNA normalized (NhTERT mRNA)
21627565In the present study, we investigated the expression of human telomerase reverse transcriptase (hTERT) and TA and their regulation, as well as apoptotic rates and correlation with the presence of human epidermal growth factor receptor 2 (HER2), in irradiated tumour-derived breast cancer cells
21627565MATERIALS AND METHODS: In 50 breast cancer tissue samples hTERT mRNA expression and TA were correlated with cell features (HER2, Estrogen and Progesterone Receptor status)
21627565HER2 was found to mediate hTERT expression through activation of Nuclear Factor-kappa B (NF-kappaB) and c-myc
21619941The relative expression of telomerase reverse transcriptase (TERT) was determined by quantitative real-time PCR
21619941Expression levels of TERT was measured in seven organs (ovary, testis, liver, gill, brain, heart, skin) from X
21619941TERT gene expression was significantly higher in ovary and testis, while all other organs showed low relative TERT expression
21619941Detectable increases in TERT expression were found in skin samples upon UVB exposure
21527554SIRT1 silencing also caused telomere dysfunction-induced foci and nuclear abnormality that were clearly associated with reduced expressions of telomerase reverse transcriptase (TERT), and PTOP, which is a member of the shelter in complex
21527554Ectopic expression of either TERT or PTOP in SIRT1-depleted cells significantly restored cell proliferation
21418545Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy
21174371Study of telomerase reverse transcriptase (hTERT) expression in normal, aged, and photo-aged skin
21174371We aimed to study human telomerase reverse transcriptase (hTERT) expression in normal, aged and photo-aged skin and to investigate its possible role in the pathogenesis of aging and photo-aging
21174371METHODS: hTERT expression using immunohistochemistry was studied in 75 subjects comprising four groups: group I, 10 subjects with aged skin; group II, 20 subjects with photo-aging; group III, Five patients with XP; and group IV, 40 subjects comprising the control groups
21174371RESULTS: We found positive hTERT in normal skin and in the basal and sometimes in supra-basal layers
21174371We reported positive hTERT expression in dermal fibroblasts, histiocytes, and skin appendages (other than hair follicles) in some cases from all the studied groups
21174371Photo-aged and prematurely photo-aged skin showed greater hTERT expression than young and aged skin
21167227Five immortalized rat pancreatic beta cell clones transduced with pLCRSTP, and six immortalized rat pancreatic beta cell clones co-transduced with pLCRSTP and another vector encoding the human telomerase reverse transcriptase (hTERT) gene, were obtained, respectively
21167227The Cre-ER protein could be induced to translocate from the cytoplasm to the nucleus by 4-hydroxytamoxifen to make SV40LTAg, hTERT and the Cre-ER gene itself excise without a secondary gene transfer
21106948Telomerase activation in atherosclerosis and induction of telomerase reverse transcriptase expression by inflammatory stimuli in macrophages
21106948METHODS AND RESULTS: We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT)
21106948Reporter and chromatin immunoprecipitation assays identified a previously unrecognized nuclear factor-kappaB (NF-kappaB) response element in the TERT promoter, to which NF-kappaB is recruited during inflammation
21106948Inhibition of NF-kappaB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-kappaB target gene
21106948Furthermore, functional experiments revealed that TERT deficiency results in a senescent cell phenotype
21106948Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in low-density lipoprotein receptor-deficient mice
21106948CONCLUSIONS: These results characterize TERT as a previously unrecognized NF-kappaB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis
21106948This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis
20969773RESULTS: BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous bTERT (bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere
20943973HPV type 16 (HPV16) E6 interacts with endogenous proteins to activate hTERT, the catalytic subunit of telomerase, thus avoiding cellular senescence signals
20943973HPV16 E6 affects hTERT expression posttranscriptionally through NFX1-123, as NFX1-123 interacts with hTERT mRNA and stabilizes it, leading to greater telomerase activity
20943973The PAM2 motif of NFX1-123, with which it binds PABPCs, is required for the posttranscriptional regulation of hTERT by HPV16 E6 and NFX1-123
20943973Here, we show that PABPCs are critical in hTERT regulation by HPV16 E6
20943973Although the amount and cellular localization of PABPCs were largely unchanged in cervical cancer cell lines with or without HPV16 and in human foreskin keratinocytes (HFKs) with or without HPV16 E6, knockdown of PABPCs decreased hTERT mRNA and telomerase activity and overexpression of PABPC4 increased these in HPV16 E6-expressing HFKs
20943973In contrast, knockdown of PABPCs in C33A cells had no effect on hTERT mRNA or telomerase activity
20943973Additionally, overexpression of PABPC4 and hTERT led to greater growth of cultured HPV16 E6-expressing HFKs
20943973This is the first evidence that PABPCs have a targeted role in hTERT regulation leading to a growth advantage in cells expressing HPV16 E6
20938386Total RNA isolated from these samples was used to measure the gene expression of p16INK4a, RB, cyclin D1, CDK4, PTEN, p27KIP, p19ARF, p21, TERT, and RAGE by real-time polymerase chain reaction assay
20938386The increased cyclin D1 mRNA level was statistically significant only at the ninth month following amputation; CDK4 and TERT mRNA levels were downregulated to a similar extent at both points compared with nonamputated controls
20824140We used miRNA microarrays to provide a detailed account of miRNA profiles for early passage and senescent human foreskin (BJ) fibroblasts as well as early and late passage immortalized fibroblasts (BJ-hTERT) that stably express the human telomerase reverse transcriptase subunit hTERT
20824140The discovery that miRNA expression is impacted by expression of ectopic hTERT as well as extended passaging in immortalized fibroblasts contributes to a comprehensive understanding of the connections between telomerase expression, senescence and processes of cellular aging
20621064Human chromosome 5 carries a transcriptional regulator of human telomerase reverse transcriptase (hTERT)
20621064Increased telomerase activity is correlated with upregulation of telomerase reverse transcriptase (TERT) expression
20621064In most human somatic cells, hTERT expression is suppressed by multiple factors
20621064However, the function of the transcriptional regulator of TERT on this chromosome remains unclear
20621064To examine the functional role of a putative hTERT regulator(s) on this chromosome, we transferred human chromosome 5 in a human melanoma cell line, A2058 cells by microcell-mediated chromosome transfer (MMCT)
20621064Moreover, this phenomenon was accompanied by a reduction of hTERT expression and telomerase activity
20621064Most importantly, we found that transcriptional suppression of hTERT by the introduction of chromosome 5 is largely mediated by regulating hTERT promoter activity
20621064Furthermore, the hTERT promoter region between -1623 and -1047 was responsible for this function
20621064These results provide evidence that transcriptional regulator(s) of the hTERT is carried on human chromosome 5 as an endogenous mechanism of hTERT suppression
20569236We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells
20569236Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes
20569236Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal
20350645Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length
20350645Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry
20350645Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups
20139322Telomerase, via its catalytic component telomerase reverse transcriptase (TERT), extends telomeres of eukaryotic chromosomes
20139322Telomerase activity was modulated in hCMEC/D3 cells via small interfering RNA-targeting human TERT (hTERT) or by using a specific pharmacological inhibitor of telomerase, TAG-6
20139322The inhibition of hTERT resulted in the upregulation of HIV-1-induced overexpression of intercellular adhesion molecule-1 via the nuclear factor-kappaB-regulated mechanism and induced the transendothelial migration of HIV-1-infected monocytic U937 cells
20139322In addition, the blocking of hTERT activity potentiated a HIV-induced downregulation of the expression of tight junction proteins
20139322Further studies revealed that the upregulation of matrix metalloproteinase-9 is the underlying mechanisms of disruption of tight junction proteins in hCMEC/D3 cells with inhibited TERT and exposed to HIV-1
20098422The guanine (G)-rich strand of telomeric DNA, usually elongated by the telomerase reverse transcriptase, can form a higher-order structure known as a G-quadruplex in vitro and in vivo
20089117The enzyme is primarily nuclear where it elongates telomeres, but many reports show that the catalytic component of telomerase (in humans called hTERT) also localizes outside of the nucleus, including in mitochondria
20089117Shuttling of hTERT between nucleus and cytoplasm and vice versa has been reported, and different proteins shown to regulate such translocation
20089117In this study we report that mutations that disrupt the nuclear export signal (NES) of hTERT render it nuclear but unable to immortalize cells despite retention of catalytic activity in vitro
20089117We find that cells expressing the mutant hTERT produce high levels of mitochondrial reactive oxygen species and have damage in telomeric and extratelomeric DNA
20089117Dysfunctional mitochondria are also observed in an ALT (alternative lengthening of telomeres) cell line that is insensitive to growth arrest induced by the mutant hTERT showing that mitochondrial impairment is not a consequence of the growth arrest
20089117Our data indicate that mutations involving the NES of hTERT are associated with defects in telomere maintenance, mitochondrial function and cellular growth, and suggest targeting this region of hTERT as a potential new strategy for cancer treatment
20080172The first mammalian enzyme with such activity has only now emerged and surprisingly consists of the catalytic subunit of telomerase (hTERT) together with RMPR, an alternative RNA component
20069564These differences could be explained by differing levels of the telomerase subunit, TERT, in SUV39h- and LMNA-deficient fibroblasts
20053783Treatment with S2T1-6OTD reduced the mRNA and protein expressions of c-Myc and hTERT, which is transcriptionally regulated by c-Myc, and decreased the activities of both genes
20052289Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene
20052289Here, we report that increased levels of IFI16 protein in normal HDFs and in HeLa cells negatively regulate the expression of human telomerase reverse transcriptase (hTERT) gene
20052289METHODOLOGY/PRINCIPAL FINDINGS: We optimized conditions for real-time PCR, immunoblotting, and telomere repeat amplification protocol (TRAP) assays to detect relatively low levels of hTERT mRNA, protein, and telomerase activity that are found in HDFs
20052289Using the optimized conditions, we report that treatment of HDFs with inhibitors of cell cycle progression, such as aphidicolin or CGK1026, which resulted in reduced steady-state levels of IFI16 mRNA and protein, was associated with increases in hTERT mRNA and protein levels and telomerase activity
20052289In contrast, knockdown of IFI16 expression in cells increased the expression of c-Myc, a positive regulator of hTERT expression
20052289Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc-mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady-state levels of c-Myc and hTERT
20052289CONCLUSIONS/SIGNIFICANCE: These data demonstrated that increased levels of IFI16 protein in HDFs down-regulate the expression of hTERT gene
22073357Since ribonucleoprotein Telomerase (TERT), catalyzing the replication of the ends of eukaryotic chromosomes, promotes cardiac muscle cell proliferation, hypertrophy and survival, here we investigated its role in the events regulating apoptosis occurrence and life span in hearts deriving from young and old rats exposed to hypoxia
22073357TERT expression lowers either in the hypoxic young, either in the old in both experimental conditions, with respect to the normoxic young
22073357Moreover, by preventing TERT enzyme down-regulation, cell cycle exit and apoptosis occurrence could be delayed and new possibilities for intervention against cell ageing and hypoxia could be opened
20034955The N-terminus of hTERT contains a DNA-binding domain and is required for telomerase activity and cellular immortalization
20034955The ability of telomerase to elongate single-stranded telomeric DNA depends on the reverse transcriptase domain of TERT, and also relies on protein:DNA contacts outside the active site
20034955Thus, the interactions of hTEN with telomere DNA and the C-terminus of hTERT are functionally separable from the role of hTEN in telomere elongation activity in vitro and in vivo, suggesting other roles for the protein and nucleic acid interactions of hTEN within, and possibly outside, the telomerase catalytic core
20007091Since ribonucleoprotein Telomerase (TERT), catalyzing the replication of the ends of eukaryotic chromosomes, promotes cardiac muscle cell proliferation, hypertrophy and survival, here we investigated its role in the events regulating apoptosis occurrence and life span in hearts deriving from young and old rats exposed to hypoxia
20007091TERT expression lowers either in the hypoxic young, either in the old in both experimental conditions, with respect to the normoxic young
20007091Moreover, by preventing TERT enzyme down-regulation, cell cycle exit and apoptosis occurrence could be delayed and new possibilities for intervention against cell ageing and hypoxia could be opened
19948976Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity
19885868Moreover, IFI 16 and hTERT co-localised within the nucleus and these two proteins physically interacted in vivo and in vitro
19885868Together, these data suggest that IFI 16 may act as an endogenous regulator of telomerase activity and, through its interaction with hTERT, contributes to the inhibition of proliferation and induces a senescence-like state
19707384Functional and gene expression analysis of hTERT overexpressed endothelial cells
19707384Human telomerase reverse transcriptase (hTERT) overexpression is thought to lead to resistance to apoptosis and oxidative stress
19707384We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro
19707384High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture
19707384Also, angiogenic responses were observed in hTERT over-expressed endothelial cell
19653337Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine
19653337Relative expression level of the catalytic subunit of telomerase (hTERT) gene and P-glycoprotein (pgp) were estimated using semi-quantitative real-time reverse transcription-PCR (RT-PCR)
19653337CONCLUSION: Chelidonine reduces telomerase activity through down-regulation of hTERT expression
19580824The third shared locus (near TERT), may be involved in telomerase activity and is associated with several environmentally caused age-related cancers
19566833This is achieved by upregulating the telomerase reverse transcriptase (TERT) gene in a temporal and spatial manner
19566820Furthermore, selective gene silencing of vascular endothelial growth factor and/or the telomerase catalytic subunit (i
19419346The TERT (telomerase reverse transcriptase) subunit of telomerase is an intensively studied macromolecule due to its key importance in maintaining genome integrity and role in cellular aging and cancer
19419346In an effort to provide an up-to-date overview of the topic, we discuss the structure of TERT genes, their alternative splicing products and their functions
19369050We used human IMR-90 lung fibroblasts and immortalized IMR-90 cells overexpressing human telomerase (hTERT) in order to examine histone biotinylation in young and senescent cells
19347296PBMCs were stimulated with antigens, and then infected with a murine leukemia virus-based retroviral vector carrying an immortalizing gene, the human telomerase-reverse transcriptase gene
19279193Furthermore, PKC-delta was shown to function in human telomerase reverse transcriptase (hTERT) gene repression
19279193These results indicate that PKC-delta plays a key role in cellular senescence programs, and suggest that the induction of senescence and hTERT repression are coordinately regulated by PKC-delta
19272180Here, we show that ectopic expression of hTERT stimulates telomerase activity and prevents accelerated senescence in G6PD-deficient cells
19272180In addition, we provide evidence that ectopic expression of hTERT attenuates the increased sensitivity of G6PD-deficient fibroblasts to oxidant-induced senescence
19272180These results suggest that ectopic expression of hTERT, in addition to acting in telomere length maintenance by activating telomerase, also functions in regulating senescence induction
19264125Up-regulation of hTERT is most likely responsible for the high levels of telomerase activity in primary ESFT, although telomerase activity and expression of hTERT are not predictive of outcome
19235838Telomerase reverse transcriptase, the key component of telomerase essential for cellular immortalization, was also inhibited in the FoxM1-depleted cells
19193721Human telomerase reverse transcriptase (hTERT) is central to maintain telomeres for continuous cell proliferation, but it remains unknown how extracellular cues regulate telomerase maintenance of telomeres
19193721Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces Smad3 phosphorylation, nuclear translocation, and hTERT gene repression
19193721Mutation of BMPRII receptor, but not TGFbetaRII, ACTRIIA, or ACTRIIB, blocked BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres, and continued cell proliferation
19193721Expression of hTERT inhibits BMP7-induced breast cancer cell senescence and apoptosis
19193721Thus, our data suggest that BMP7 induces breast cancer cell aging and death by a mechanism involving inhibition of telomerase activity and telomere maintenance via BMPRII receptor- and Smad3-mediated repression of the hTERT gene
19070423Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance
19056671Once formed, telomere aggregates showed colocalization with gamma-H2AX but not with TERT, suggesting that telomere aggregates are sites of DNA damage
19023015Of interest, both estrogen and NO signaling, specifically through the estrogen receptor-alpha (ERalpha) and the endothelial isoform of the nitric oxide synthase (eNOS), have been shown to counteract endothelial senescence through a shared downstream effector, the catalytic subunit of human telomerase (hTERT), a key molecule in the aging process
19023015Since aging is the first and most relevant risk factor in cardiovascular diseases, it is tempting to speculate that hTERT may be at the cross point between the NO and estrogen pathways
19023015The present review will focus on the evolutionary and molecular aspects linking eNOS, ERs, and hTERT in counteracting the process of endothelial cell aging
19003240Regulation of hTERT transcription: a target of cellular and viral mechanisms for immortalization and carcinogenesis
19003240The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a major mechanism that negatively and positively controls telomerase activity in normal and cancer cells, respectively
19003240A growing body of data suggests that various cellular and viral factors and pathways involved in cell senescence, immortalization and carcinogenesis act on the hTERT promoter
19003240The activity of the hTERT promoter is regulated, either directly or through signaling pathways, by oncogene products (e
19003240Endogenous factors involved in the physiological repression of the hTERT gene have also been revealed by chromosome transfer experiments
19003240The integration of viral genomes in the hTERT locus can lead to hTERT activation and telomerase induction
19003240Here, we summarize these findings and pay special attention to recent findings with relevance to the endogenous regulatory mechanisms of hTERT transcription
18938767METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on biopsy specimens from 11 mild, 11 moderate and 12 severe active inflammation of UC cases and from 10 normal colonic tissue cases
189387678%; TERT/TP-1: 2
18938767In severe inflammation, all parameters showed decreased epithelial expression; IGF1R showed decreased mRNA expression, while HGFR was overexpressed and TERT showed a decreased tendency
18938767CONCLUSIONS: The epithelial expression of IGF1R, HGFR and TERT/TP-1 is elevated in mildly active UC
18845559Retroviral-mediated Cdx2 expression in immortalized human esophageal keratinocytes [EPC-human telomerase reverse transcriptase (hTERT)] could transiently be established but not maintained and was associated with a reduction in cell proliferation
18836295Human telomerase reverse transcriptase (hTERT) is the rate-limiting factor of telomerase activity and also ASODN (antisense oligodeoxynucleotides) targeting to hTERT gene represent a promising approach to tumor therapy
18836295The purpose of this study was to investigate the effects of nanosize delivery system for antisense oligonucleotide for hTERT in vitro on EC9706 cells and in vivo on tumor tissue
18672169METHODS: C57/Bl6 wild-type, endothelial nitric oxide synthase (eNOS)-deficient and telomerase reverse transcriptase (TERT)-deficient mice were randomized to voluntary running or no running wheel conditions (n = 8 to 12 per group)
18672169The exercise-induced changes were absent in both TERT(-/-) and eNOS(-/-) mice
18672169Up-regulation of telomere-stabilizing proteins by physical exercise in mice reduced doxorubicin-induced p53 expression and potently prevented cardiomyocyte apoptosis in wild-type, but not in TERT(-/-) mice
18672169These beneficial cardiac effects are mediated by TERT, eNOS, and IGF-1
18650388We therefore generated mouse telomerase reverse transcriptase (mTert)-GFP-transgenic mice and assayed the ability of mTert-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine
18466174Expression of human telomerase reverse transcriptase in bone marrow CD34+ cells from patients with beta-thalassemia major
18466174Human telomerase reverse transcriptase (hTERT) is a rate-limiting enzyme that dictates the activity of human telomerase and thus decides the life span of cells
18466174The expression of hTERT and its roles in beta-thalassemia major are unclear, however
18466174STUDY DESIGN AND METHODS: hTERT mRNA expression in bone marrow (BM) CD34+ cells from 25 children with beta-thalassemia major and 15 control subjects was investigated using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis
18466174The relationship between hTERT and sEPO as well as Hb was then examined
18466174RESULTS: It was found that hTERT mRNA expression was significantly up regulated in BM CD34+ cells from patients with beta-thalassemia major
18466174Furthermore, a significantly positive correlation was found between hTERT mRNA and sEPO (r = 0
18466174A significantly inverse correlation, however, was found between hTERT mRNA and Hb concentration (r = -0
18466174CONCLUSION: Our findings suggest that severe anemia with low Hb concentration might up regulate hTERT expression of BM CD34+ cells and sEPO levels in patients with beta-thalassemia major
18454043Compounds currently under development that seek to inhibit hTERT, the reverse transcriptase component of telomerase, include nucleoside analogs and the small molecule BIBR1532
18452712To investigate the molecular mechanism behind the cellular senescence of hBMMSCs, microarray analysis was used to compare the expression profiles of early passage hBMMSCs, late passage hBMMSCs and hBMMSCs ectopically expressing human telomerase reverse transcriptase (hTERT)
18358537To facilitate long-term cultivation, we immortalized porcine olfactory neuronally restricted progenitor cells by genomic insertion of a cDNA encoding the catalytic subunit of the human telomerase reverse transcriptase (hTERT) yielding a stable neuroblast subclone (OBGF400)
18229711Despite its importance, a high-resolution structure of the telomerase enzyme has been elusive, although a crystal structure of an N-terminal domain (TEN) of the telomerase reverse transcriptase subunit (TERT) from Tetrahymena has been reported
18229711In this study, we used a comparative strategy, in which sequence-based machine learning approaches were integrated with computational structural modeling, to explore the potential conservation of structural and functional features of TERT in phylogenetically diverse species
18229711We generated structural models of the N-terminal domains from human and yeast TERT using a combination of threading and homology modeling with the Tetrahymena TEN structure as a template
18212065Circle formation in WS cells is reduced by reconstitution with wild-type WRN but not mutant forms lacking either exonuclease or helicase activity, demonstrating that both enzymatic activities of WRN are required to suppress telomeric-circle formation in normal cells expressing telomerase reverse transcriptase
18158869Promotion of cell proliferation by HBXIP via upregulation of human telomerase reverse transcriptase in human mesenchymal stem cells
18158869Telomerase activity is known to be critical in cellular senescence and its level is modulated by the regulation of the telomerase catalytic subunit, telomerase reverse transcriptase (TERT), at both the transcriptional and post-transcriptional levels
18158869To investigate the mechanism of promoting proliferation by HBXIP, the effect of HBXIP on human TERT (hTERT) was investigated in human mesenchymal stem cells (hMSC)
18158869METHODS: BMMS-03 cells and hMSC from the bone marrow of a 4-month-old elicited fetus, were transiently transfected with the pcDNA3-hbxip plasmid encoding the HBXIP gene and pSilencer-hbxip plasmid encoding RNA interference (RNAi) targeting HBXIP mRNA, followed by the examination of the hTERT promoter reporter gene by luciferase assay, and the detection of telomerase activity by telomeric repeat amplication protocol, respectively, as well as the expression levels of hTERT, c-Myc, and Bcl-2 by Western blot analysis
18158869RESULTS: The overexpression of HBXIP led to a significant upregulation of hTERT promoter activity, telomerase activity, and the expression levels of hTERT, c-Myc, and Bcl-2 in BMMS-03 cells
18158869CONCLUSION: Our data demonstrated that HBXIP significantly stimulated the transcription and expression of hTERT and increased the activity of telomerase in BMMS-03 cells, which provides a new insight into the mechanism of promoting cell proliferation by HBXIP
18157659Molecular cloning and characterization of the zebrafish (Danio rerio) telomerase catalytic subunit (telomerase reverse transcriptase, TERT)
18157659Telomerase is an enzyme composed of a catalytic subunit (TERT) and RNA template (TR), which specifically elongates telomeres and prevents cellular senescence
18157659To facilitate the investigation of telomerase function in the teleost visual system, the coding sequence of zebrafish TERT is revealed and cloned
18157659Based on the amino acid sequence of mouse TERT, a full-length telomerase reverse transcriptase cDNA of zebrafish has been isolated and cloned
18157659Multiple alignment shows that the protein sequence contains the conserved motifs and residues found in TERT of other species
18157659RT-PCR and TRAP assay has detected TERT mRNA expression and telomerase activity, respectively, in all tissues examined, including the retina and the brain
18157659Immunohistochemistry reveals that most neurons in zebrafish retina express TERT in the cell nucleus
18157659The expression of telomerase activity and TERT in retina implies that telomerase has functions other than the elongation of telomere
18157152Its protein subunit TERT is highly conserved among eukaryotes, whereas the RNA subunit varies greatly in size and sequence, hindering the identification of telomerase RNAs in some important model organisms
18084761The expression levels of telomerase catalytic subunit hTERT and oncogenic MYC in essential thrombocythemia are affected by the molecular subtype
18084761The role of telomerase catalytic subunit hTERT in clonal malignancies including human leukemia is fundamental in overcoming cell senescence and enabling prolonged proliferation
18084761One direct transcriptional activator of hTERT is the oncogene MYC which is known to be, in turn, activated by JAK2
18084761To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV)
18084761We could determine an up-regulation of MYC expression exclusively in JAK2(wt) ET, whereas hTERT expression was rather inconsistent across the groups
18084761Interestingly, a significant correlation between MYC and hTERT expression could only be established in homozygous JAK2(V617F) PV and control cases
18084761Thus, the functional link between MYC and hTERT seems to be impaired depending on the molecular ET subtype, which in turn may have implications on the phenotype and course of the disease
18058552Structural insight into the hTERT intron 6 sequence d(GGGGTGAAAGGGG) from 1H-NMR study
18058552In addition to their presence in telomeres, where they may play a role in maintaining the stability and integrity of chromosomes, guanine-rich regions are found in other region of the genome, amongst these is intron 6 of hTERT a gene codifying for the enzyme telomerase
18058552Interestingly, the formation of G-quadruplexes in this region is involved in the down-regulation of telomerase activity caused by an alteration of the hTERT splicing pattern
18027880Stabilization of cellular properties and differentiation mutilpotential of human mesenchymal stem cells transduced with hTERT gene in a long-term culture
18027880Human telomerase catalytic subunit (hTERT) gene transduction can prolong the life span of hMSCs and maintain their potential of osteogenic differentiation
18027880We established a line of hMSCs transduced with exogenous hTERT (hTERT-hMSCs) and investigated its sustaining cellular properties in a long-term culture
17991312This study was to determine the effect of tankyrase antisense oligonucleotide (asTANKS) combined human telomerase reverse transcriptase antisense oligonucleotide (ashTERT) on telomere dynamics in human lung adenocarcinoma A549 cells
17991312METHODS: A549 cells were transfected with ashTERT, asTANKS, ashTERT combined asTANKS, and human telomerase reverse transcriptase sense oligonucleotide (shTERT), tankyrase sense oligonucleotide (sTANKS), or blank vector as control
17991312The expression of hTERT mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR)
17991312RESULTS: The mRNA level and telomerase activity of hTERT in A549 cells were strongly suppressed by ashTERT, but not by asTANKS; while tankyrase activity was significantly inhibited by asTANKS, not by ashTERT
17986575Recent studies suggest that the Ets transcription factor family, downstream of the mitogen signaling pathways of MAP kinase, regulates telomerase activity at the gene transcription level of human telomerase reverse transcriptase (hTERT)
17986575Several Ets transcription factors are involved in regulating hTERT gene expression, both directly and indirectly through the proto-oncogene c-myc
17986575Ets2 may also play an important role in regulating the hTERT gene; but further studies are required to decipher the mechanisms in the regulation of telomerase activity
17943236Molecular mechanisms involved in endothelial cell aging: role of telomerase reverse transcriptase
17943236Important players in the process of endothelial cell aging are reactive oxygen species, nitric oxide bioavailability, mitochondrial integrity and the activity of telomerase reverse transcriptase
17673177Site-specific methylation of CpG nucleotides in the hTERT promoter region can control the expression of hTERT during malignant progression of colorectal carcinoma
17673177Expression of hTERT has been recognized an important factor in cellular aging and immortalization
17673177Therefore, to analyze regulatory mechanism of hTERT expression, we investigated the CpG methylation pattern of the hTERT promoter as an epigenetic mechanism and its implication in transcriptional regulation of hTERT using tissues of colorectal carcinoma
17673177As a result, we were able to observe an increased pattern of hTERT expression according to the malignant progression of colorectal carcinoma
17673177Additionally, we could find that hTERT expression was induced when the P1 and P2 region of hTERT were sufficiently hypermethylated and, oppositely, the G1 region of hTERT was hypomethylated
17673177Importantly, we could find three specific CpG sites (7th CpG of P2 and 11th and 2nd-10th CpGs of P1) closely related with the increasing of hTERT expression
17673177These findings may provide important clues to deducing the expression mechanisms of hTERT
17662305Synergistic activation of extracellular signal-regulated kinase in human dermal fibroblasts by human telomerase reverse transcriptase and transforming growth factor-beta1
17662305BACKGROUND: Human telomerase reverse transcriptase (hTERT) is primarily known for its ability to elongate telomeres for maintaining chromosomal integrity and delaying cellular senescence
17662305Recently, hTERT has emerged as having a role in promoting cellular proliferation that is independent of telomere elongation
17662305How hTERT elicits this novel function is a fundamental question in cell biology
17662305MATERIALS AND METHODS: Primary HDFs were transfected with either recombinant adenovirus expressing hTERT (Ad-hTERT) or control adenovirus (Ad-NULL) and subsequently treated with TGF-beta1 (2 pg/mL)
17634580Telomerase is a ribonucleoprotein complex composed minimally of telomere reverse transcriptase gene (hTERT) and RNA template (hTR), and its enzyme activity in cells is primarily limited by the level of hTERT expression
17634580Therefore, telomerase activity in cells can be reconstituted by overexpression of hTERT, frequently resulting in extension of replicative life span or immortalization
17634580In this article, we discuss the detailed methods to extend the in vitro replicative life span of primary human cells by ectopic expression of hTERT
17559502Cellular senescence in human myoblasts is overcome by human telomerase reverse transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and therapeutic strategies for muscular dystrophies
17460194Knocking down p53 with siRNA does not affect the overexpression of p21WAF-1 after exposure of IMR-90 hTERT fibroblasts to a sublethal concentration of H2O2 leading to premature senescence
17411379Transduction with human telomerase reverse transcriptase immortalizes a rhesus macaque CD8+ T cell clone with maintenance of surface marker phenotype and function
17411379Expression of telomerase reverse transcriptase (TERT) in differentiated cells can maintain telomere length over many cell divisions, preventing senescence
17411379We used a retroviral vector that expresses the human TERT (hTERT) gene to transduce a rhesus macaque-derived CD8(+) T cell clone specific for the MamuA*01-restricted immunodominant SIV gag epitope CM9
17352650We observed an inverse expression pattern between the osteogenic master regulatory gene, CBFA1, and the stem cell-associated gene, hTERT
17352650We showed that Cbfa1 acts as a partial repressor of TERT, which may facilitate cellular differentiation
17352650This study examined whether Cbfa1 was capable of regulating the promoter of the early stem cell-associated gene, telomerase reverse transcriptase (TERT)
17352650CBFA1 and TERT gene expression was assessed by real-time PCR
17352650The functional capacity of Cbfa1 to bind to the hTERT promoter was performed using a modified electrophoretic mobility shift assay (EMSA)
17352650Chromatin immunoprecipitation (ChIP) analysis was used to examine Cbfa1 binding to the hTERT promoter in vivo
17352650Functional analysis of CBFA-1 wildtype and mutant DNA binding sites on TERT promoter fragments was assessed using the promoterless green fluorescence protein (GFP) reporter vector, pEGFP-1, after transfection into HOS cells
17352650RESULTS: This study showed an inverse expression pattern between the osteogenic master regulatory gene, CBFA1, and the stem cell-associated gene, hTERT
17352650The data showed that BMSSCs undergo osteogenic commitment after the loss of hTERT expression, with concomitant elevated levels of CBFA1 transcripts
17352650In addition, two unique Cbfa1 DNA binding sites were identified on the hTERT proximal promoter by EMSA supershift assay
17352650ChIP analysis showed that Cbfa1 interacted directly with the hTERT promoter in vivo
17352650Functional studies using GFP reporter constructs, driven by 2- and 3-kbp hTERT proximal promoter fragments, showed significantly lower levels of transcriptional activity compared with corresponding constructs with mutated Cbfa1 binding site Oligo 2
17352650CONCLUSIONS: These studies suggest that Cbfa1 may act as a repressor of early stem cell markers such as hTERT as one possible mechanism for facilitating cellular differentiation
17325661In human cells, telomerase activity is tightly regulated by the expression of its catalytic subunit, namely, the human telomerase reverse transcriptase (hTERT)
17325661However, the molecular mechanisms involved in the regulation of hTERT expression have not been completely clarified
17325661We have previously reported that transforming growth factor beta (TGF-beta) represses the expression of the hTERT gene
17210516We examined the expression of telomeric DNA in 21 atypical adenomatous hyperplasias (AAHs) and 40 bronchioloalveolar carcinomas (BACs) measuring 2 cm or less in greatest diameter using fluorescent in situ hybridization and the expression of human telomerase reverse transcriptase (hTERT) messenger RNA (mRNA) in 35 AAHs and 37 BACs
17210516In "benign" lung samples, the pattern of expression of hTERT mRNA was barely detected in the nonciliated cells of the bronchioles and alveolar type II cells
17210516Positive expression of hTERT mRNA was recognized in 66% of AAHs and 97% of BACs
17075048The physiological concentration of 17beta-estradiol activated hTERT, decreased SA-beta-gal-positive cells, and caused cell proliferation
17066600MATERIALS AND METHODS: I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue
16951325In this study, we show that early passage T cell clones transduced or not with human telomerase reverse transcriptase displayed identical growth rates upon mitogenic stimulation and no marked global changes in gene expression
16798746Telomerase activity is known to be critical in cellular senescence and its level is modulated by regulation of telomerase catalytic subunit (telomerase reverse transcriptase (TERT)) at both the transcriptional and post-transcriptional levels
16798746Raloxifene, like estrogen, clearly induced the telomerase activity and human TERT (hTERT) expression via estrogen receptor (ER) alpha and ERbeta
16798746In addition, raloxifene induced both the phosphorylation of hTERT and IkappaB
16798746Moreover, cotreatment with an IkappaBalpha phosphorylation inhibitor, BAY-11-7082, or a specific NFkappaB nuclear translocation inhibitor, SN50, significantly attenuated the raloxifene-induced telomerase activity and the association of NFkappaB with hTERT
16798746These results show that raloxifene induced the up-regulation of telomerase activity not only by the transcriptional regulation of hTERT but also by post-translational regulation of the phosphorylation of Akt and hTERT and the association of hTERT with NFkappaB in HUVECs
16756500The structure and function of telomerase reverse transcriptase
16756500Structurally, telomerase reverse transcriptase (TERT) contains unique and variable N- and C-terminal extensions that flank a central RT-like domain
16756500Two distinguishing features of TERT are its stable association with the telomerase RNA and its ability to repetitively reverse transcribe the template segment of RNA
16756500Here we discuss TERT structure and function; its regulation by RNA-DNA, TERT-DNA, TERT-RNA, TERT-TERT interactions, and TERT-associated proteins; and the relationship between telomerase enzymology and telomere maintenance
16717406AST cells demonstrated functional impairment of telomerase due to perturbed subcellular localization of human telomerase reverse transcriptase, suggesting that mild oxidative stress might affect the cell fate of cancer cells
16621759Using normal swine kidney epithelial (SKE) cells that were shown to be senescent at passages 12 to 14, we have established one lifespan-extended cell line and two lifespan-extended cell lines by exogenous introduction of the human catalytic subunit of telomerase (hTERT) and simian virus 40 large T-antigen (SV40LT), all of which maintain epithelial morphology and express cytokeratin, a marker of epithelial cells
16613901We have previously shown that the protein subunit of telomerase, hTERT, has a bonafide N-terminal mitochondrial targeting sequence, and that ectopic hTERT expression in human cells correlated with increase in mtDNA damage after hydrogen peroxide treatment
16613901In this study, we show, using a loxP hTERT construct, that this increase in mtDNA damage following hydrogen peroxide exposure is dependent on the presence of hTERT itself
16613901Further experiments using a dominant negative hTERT mutant shows that telomerase must be catalytically active to mediate the increase in mtDNA damage
16613901Etoposide, but not methylmethanesulfate, also promotes mtDNA lesions in cells expressing active hTERT, indicating genotoxic specificity in this response
16613901Cells carrying this mutated hTERT not only have significantly reduced levels of mtDNA damage following hydrogen peroxide treatment, but strikingly also do not shown any loss of viability or cell growth
16613901Thus, localization of hTERT to the mitochondria renders cells more susceptible to oxidative stress-induced mtDNA damage and subsequent cell death, whereas nuclear-targeted hTERT, in the absence of mitochondrial localization, is associated with diminished mtDNA damage, increased cell survival and protection against cellular senescence
16504006BACKGROUND: Human cells appear exquisitely sensitive to the levels of hTERT expression, the telomerase reverse transcriptase
16504006In primary cells that do not express hTERT, telomeres erode with each successive cell division, leading to the eventual loss of telomere DNA, an induction of a telomere DNA damage response, and the onset of cellular senescence or crisis
16504006In some instances, an average of less than one appropriately spliced hTERT transcript per cell appears sufficient to restore telomerase activity and telomere maintenance, and overcome finite replicative capacity
16504006RESULTS: To underscore this sensitivity, we showed that a widely used system of transcriptional induction involving ecdysone (muristerone) led to sufficient expression of hTERT to immortalize human fibroblasts, even in the absence of induction
16504006To permit tightly regulated expression of hTERT, or any other gene of interest, we developed a method of transcriptional control using an invertible expression cassette flanked by antiparallel loxP recombination sites
16504006Upon inversion of the hTERT cDNA to a transcriptionally competent orientation via the action of Cre recombinase, cells acquired telomerase activity, telomere DNA was replenished, and the population was immortalized
16435298Telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) function together to elongate telomeres and to protect chromosomal ends
16421168Ectopic over-expression of hTERT homogenized both allelic and chromosome-specific telomeric distributions
16308915The current studies were designed to characterize the accelerated senescence response to radiation in the breast tumour cell in terms of its dependence on functional p53 and its relationship to telomerase activity, telomere lengths, expression of human telomerase reverse transcriptase (hTERT, the catalytic subunit of telomerase) and human telomerase RNA (hTR, the RNA subunit of telomerase), as well as the induction of cytogenetic aberrations
16308915Studies were performed in p53 wild-type MCF-7 cells, MCF-7/E6 cells with attenuated p53 function, MDA-MB231 cells with mutant p53 and MCF-7/hTERT cells with constitutive expression of hTERT
16308915Radiation did not suppress expression of either hTERT or hTR, alter telomerase activity or induce telomere shortening
16308915Accelerated senescence in response to ionizing radiation is p53 dependent and associated with telomer dysfunction but is unrelated to changes in telomerase activity or telomere lengths, expression of hTERT and hTR
16108763Telomerase reverse transcriptase mRNA expression in peripheral lymphocytes of patients with chronic HBV and HCV infections
16108763So far, quantification of human telomerase reverse transcriptase levels (hTERT) in PL, has not been reported
16108763We determined hTERT mRNA levels in PL of hepatitis B virus (HBV) and hepatitis C virus (HCV) patients, in an attempt to address whether hTERT transcripts in PL are altered in these viral diseases, which are characterized by immune dysfunction and increased incidence of hepatocarcinogenesis
16108763We observed significantly lower hTERT mRNA levels in HBV and HCV patients compared with healthy individuals (P < 0
16108763Also no correlation was observed between hTERT mRNA expression, and HBV and HCV replicative activity
16108763In the inactive group (n = 18) we observed a negative correlation between hTERT mRNA expression and disease duration (rs = -0
16108763We performed for the first time an accurate quantification of hTERT mRNA expression in PL of HBV and HCV patients
16108763The observed low levels of hTERT mRNA expression in the above patients may suggest its involvement in the immunopathogenesis of chronic viral hepatitis
16093915Because the expression of TERT is regulated by the PI3-K/Akt pathway, we examined the effect of 17beta-estradiol on Akt activity in EPCs
15976917The promoter for human telomerase reverse transcriptase (hTERTp) is preferentially active in malignant cells
15965488We have developed a meningioma cell line by retrovirally transducing primary cells derived from a human WHO grade I meningothelial meningioma with the human telomerase reverse transcriptase (hTERT) gene, which enables bypassing cellular senescence
15965488Quantitative RT-PCR and a telomeric repeat amplification protocol (TRAP) assay revealed high hTERT mRNA levels and high telomerase activity in all transduced populations, while nontransduced cells were negative
15964568Comparison of early passage, senescent and hTERT immortalized endothelial cells
15964568Immortalization of normal human cells by ectopic expression of the catalytic subunit of human telomerase (hTERT) has shown to result in highly differentiated cell lines
15964568Therefore, we have immortalized human umbilical vein endothelial cells (HUVECs) by hTERT overexpression and compared them to their normal early passage and senescent counterparts
15964568This study, including a proteomic approach, shows that ectopic hTERT expression leads to a stable growing cell line
15849192Human telomerase reverse transcriptase immortalizes bovine lens epithelial cells and suppresses differentiation through regulation of the ERK signaling pathway
15849192We have previously demonstrated that human telomerase reverse transcriptase (hTERT) catalytic subunit is functionally compatible with a telomerase template RNA from rabbit
15849192In this study, we show that hTERT is also functionally compatible with a telomerase template RNA from bovine
15849192Introduction of hTERT into bovine lens epithelial cells (BLECs) provides the transfected cells telomerase activity
15849192The expressed hTERT in BLECs supports normal growth of the transfected cells for 108 population doublings so far, and these cells are still extremely healthy in both morphology and growth
15849192By synthesizing new telomere, hTERT prevents replicative senescence, and through regulation of MEK/ERK, protein kinase C, and protein kinase A and eventual suppression of the MEK/ERK signaling pathway, hTERT inhibits differentiation of BLECs
15849192Our finding that hTERT can suppress RAS/RAF/MEK/ERK signaling pathway to prevent differentiation provides a novel mechanism to explain how hTERT regulates cell differentiation
15769667Significant overlap between indirect telomerase regulation pathways and cell cycle checkpoint pathways exist, suggesting that these discrete genetic elements (namely, p21, p53, and hTERT) synergistically cooperate to inhibit tumorigenesis
15769667In addition, the study of stem cells gives information about the down-regulation of hTERT in the aging process
15769667Therefore, restoring telomerase activity as a putative therapeutic strategy necessitates further study to elucidate the intricacies linking genetic and epigenetic modulations of hTERT
15735037In vitro, nuclear human telomerase reverse transcriptase (hTERT) expression was drastically decreased after 24 hours, induction of cellular senescence and complete cessation of growth was seen after 15 days, paralleled by telomere shortening of ca
15735037Immunostaining of xenograft tissues showed that this response was paralleled by loss of nuclear hTERT protein expression and an increase in atypical mitoses indicative of telomere dysfunction
15735037Cytoplasmic hTERT expression and its colocalization with ubiquitin was observed suggesting that hTERT is bound to ubiquitin and targeted for enhanced degradation upon BRACO-19 treatment
15659210Cells were transduced to express the human reverse transcriptase subunit (hTERT) of telomerase
15647378UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span
15647378The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway
15520173It has recently been reported that human telomerase reverse transcriptase expression may be strongly up-regulated in human endothelial cells cocultivated with tumor cells
15520173Quantitative reverse transcription-PCR also showed a direct correlation between human telomerase reverse transcriptase expression and the proliferative index of the cultures
15326392Telomerase, whose core components are a reverse transcriptase (TERT) and an integral RNA (TERC) maintains telomere ends
15263087Most normal human somatic cells have a limited proliferative life span, and expression of the rate-limiting telomerase catalytic subunit, known as human telomerase reverse transcriptase (hTERT), has been believed to be tightly repressed
15263087This model of hTERT regulation is challenged by the recent identification of the induction of hTERT in normal cycling human fibroblasts during their transit through S phase
15263087Here we show the small-molecule-based identification of the assembly and disassembly of E2F-pocket protein-histone deacetylase (HDAC) complex as a key mechanistic basis for the repression and activation of hTERT in normal human cells
15263087A cell-based chemical screen was used to identify a small molecule, CGK1026, that derepresses hTERT expression
15263087CGK1026 inhibits the recruitment of HDAC into E2F-pocket protein complexes assembled on the hTERT promoter
15263087Chromatin immunoprecipitation analysis reveals dynamic alterations in hTERT promoter occupancy by E2F and pocket proteins according to the cell cycle-dependent regulation of hTERT
15263087Dominant-negative or protein-knockout strategies to disrupt the assembly of E2F-pocket protein-HDAC complex derepress hTERT and telomerase activity
15263087Taken together with the results on the regulatory function of these complexes in cellular senescence and tumorigenesis, our findings suggest that dynamic assembly of E2F-pocket protein-HDAC complex plays a central role in the regulation of hTERT in a variety of proliferative conditions (e
15079066Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice
15079066Telomerase is a ribonucleoprotein containing an essential telomerase RNA template and telomerase reverse transcriptase (TERT) that maintains telomeres
15079066The dosage requirements for mammalian TERT in telomere length homeostasis are not known, but are of importance in cellular senescence, stem cell renewal, and cancer
15079066Here, we characterize telomere maintenance and function upon successive breeding of mice deficient in mTert
15079066These studies reveal a unique dosage requirement for telomere length maintenance by TERT; despite haploinsufficiency for the maintenance of long telomeres, mTert+/- mice retain minimal telomere DNA at all chromosome ends and do not exhibit the infertility typical of telomerase-deficient strains
15079066Unlike the long (>50 kbp) average telomere lengths of wild-type laboratory mice, mTert+/- animals mice possess short telomere lengths similar to humans and wild-derived mice
15079066Unexpectedly, mTert+/- mice are ersatz carriers for genetic instability, because their mating led to accelerated genetic instability and infertility in null progeny
15079066Thus, limiting TERT levels play a key role in the maintenance of genome integrity, with important ramifications for the maintenance of short telomeres in human cancer and aging
15039457In cancer cell lines expressing telomerase and in pre-senescent fibroblasts ectopically expressing hTERT, this phenomenon is abrogated
14963003Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells
14963003Aging is associated with a rise in intracellular reactive oxygen species (ROS) and a loss of telomerase reverse transcriptase activity
14963003Incubation with H2O2 induced the nuclear export of telomerase reverse transcriptase (TERT) into the cytosol in a Src-family kinase-dependent manner
14963003Therefore, we investigated the hypothesis that age-related increase in reactive oxygen species (ROS) may induce the nuclear export of TERT and contribute to endothelial cell senescence
14963003Along with the enhanced formation of ROS, we detected an export of nuclear TERT protein from the nucleus into the cytoplasm and an activation of the Src-kinase
14963003Likewise, nuclear export of TERT protein, loss in the overall TERT activity, and the onset of replicative senescence were delayed by incubation with N-acetylcysteine
14719074Regulation of telomerase and its hTERT messenger in colorectal cancer
14719074The human telomerase complex is comprised of multiple components, but telomerase reverse transcriptase (hTERT) is the most important component for the control of telomerase activity
14719074To better understand if a link between hTERT/telomerase regulation and p53 status exists in colorectal carcinogenesis, we analysed 43 cases of colorectal carcinoma for hTERT mRNA expression and telomerase activity
14563552Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements
14563552Elucidation of the mechanisms governing expression of the human telomerase reverse transcriptase (hTERT) is important for understanding cancer pathogenesis
14563552Approximately 90% of tumors express hTERT, the major catalytic component of telomerase
14563552It is not clear how these transcription factors compete for the same recognition sequence in the hTERT core promoter region
14563552Studies have shown that the combined expression of SV40 large T antigen (T-Ag), hTERT, and H-Ras is able to transform human cells
14563552We transduced cells with amphotropic retroviral constructs containing SV40 T antigen, hTERT, and activated H-ras
14563552Transduced cells exhibited anchorage independence in soft agar and expressed increased levels of c-Myc and endogenous hTERT
14563552These findings indicate that the widely used model system of WI-38 fibroblasts can be employed for transformation studies using defined genetic elements and that the endogenous hTERT and c-Myc are induced in these cells during early tumorigenesis
14563552Such studies should have important implications in the mechanisms of hTERT and c-Myc induction in the beginning stages of tumorigenesis and facilitate extension of these studies to novel models of tumorigenesis in cellular senescence
14506173Antisense-mediated hTERT inhibition specifically reduces the growth of human bladder cancer cells
14506173PURPOSE: The expression of human telomerase reverse transcriptase (hTERT) is associated with cellular aging and tumorigenesis
14506173The aim of this study was to investigate whether hTERT inhibition by antisense oligodeoxynucleotides (AS-ODN) can act as an efficient strategy to specifically impair the growth of bladder cancer (BCa) cells in vitro
14506173EXPERIMENTAL DESIGN: Twenty-three AS-ODNs were designed complementary to five putative single-stranded target sites using a computer-aided secondary structure prediction of hTERT mRNA
14506173The BCa cell lines were transfected once or several times with AS-ODNs, and the influences on cell growth, hTERT mRNA, and hTERT protein levels, as well as on telomerase activity, were examined
14506173The specificity of the growth-inhibitory action of the five efficient AS-ODNs was confirmed by diminished hTERT transcript amount (< or =88%) and reduced hTERT protein content in EJ28 cells
14506173CONCLUSION: Specific hTERT inhibition causes remarkable short- and long-term effects on the growth of BCa cells and represents a promising new treatment option of solid tumors
12861050We also demonstrated that the expression of hTERT can extend the replicative life of muscle cells although these failed to undergo immortalization
12842909The overexpression of MYC in WRN syndrome fibroblasts or after WRN depletion from control fibroblasts led to rapid cellular senescence that could not be suppressed by hTERT expression
12836417Previous studies have shown that the replicative life span of various primary human cells can be prolonged by transduction of the telomerase reverse transcriptase (hTERT) gene
12836417In an attempt to overcome this barrier three groups have introduced hTERT cDNA into human T lymphocytes and monitored its effect on their life span
12836417In two of these studies, hTERT significantly extended the replicative life span of CD8+ T clones, whereas this was not the case in the third study using bulk T lymphocytes
12759390Human telomerase reverse transcriptase was sufficient to immortalize both these cell strains but not normal melanocytes
12721352To determine if chondrocyte age changes are reversible, we transfected human articular cartilage chondrocytes with the human telomerase gene (hTERT) and human papilloma virus oncogenes (E6 and E7)
12721352Transfection of human articular cartilage chondrocytes from a forty-seven-year-old donor with hTERT and human papilloma virus proto-oncogenes E6 and E7 created a cell line that has completed more than 300 population doublings as compared with an upper limit of twenty-five population doublings for normal cells
12721352Telomere length increased in cells transduced with hTERT
12678728Antisense oligonucleotides directed to human telomerase RNA, the dominant negative form of human telomerase reverse transcriptase (hTERT), hammerhead ribozymes that cut hTR and agents that interact with quadruplex DNA represent potential telomerase inhibitors
12606403Expression of the human telomerase catalytic reverse transcriptase subunit (hTERT) in these cells reconstitutes telomerase activity and immortalizes the cells without tumor transformation
12606403Expression of the human telomerase catalytic subunit restored the telomerase activity in the sheep cells and extended their proliferative life span
12569699METHODS: The pGRN145 plasmids encoding human telomerase reverse transcriptase (hTERT) were introduced into the normal human primary fibroblasts by electroporation
12569699The hTERT positive fibroblasts were then induced to form bone nodules
12569699The hTERT positive fibroblasts could form bone nodules when they were cultured in vitro induced by bone morphogentic protein 2 and tumor necrosis factor-alpha
12565825A human TERT C-terminal polypeptide sensitizes HeLa cells to H2O2-induced senescence without affecting telomerase enzymatic activity
12565825We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting
12565825Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence
12565825This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity
12565825Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress
12548976In the present work, plasmid pGRN145 bearing a cDNA insert of human telomerase reverse transcriptase (hTERT) was introduced into the fibroblasts with osteogenic potential by electroporation
12548976The stable hTERT+ fibroblast clones was established and cultured for long-term in a medium containing hygromycin-B
12548976The exogenous hTERT mRNA expression and telomerase activity were detected
12548976The hTERT+ fibroblasts showed shorter population doubling time and no beta-galactosidase stain, which indicated a stronger proliferative capacity and fewer signs of cell senescence, compared to their hTERT- counterpart
12548976These evidenced that the life-span of hTERT+ fibroblasts was extended
12393949Transfection of the telomerase reverse transcriptase gene results in elongation of telomeres and extension of lifespan
12181331Downstream E-box-mediated regulation of the human telomerase reverse transcriptase (hTERT) gene transcription: evidence for an endogenous mechanism of transcriptional repression
12181331Regulation of the hTERT gene encoding the telomerase catalytic subunit plays an important role in human cell senescence, immortalization, and carcinogenesis
12181331By examining the activity of various deleted or mutated hTERT promoter fragments, we show that an E-box element downstream of the transcription initiation site is critical to differential hTERT transcription between the telomerase/hTERT-positive renal cell carcinoma cell line (RCC23) and its telomerase/hTERT-negative counterpart containing a transferred, normal chromosome 3 (RCC23+3)
12181331This E-box element mediated repression of hTERT transcription in RCC23+3 but not in RCC23
12135889Transfection of cells with expression vectors containing the human telomerase reverse transcriptase (hTERT) maintains telomere length and effectively gives normal cells an unlimited life span in culture
12135889In addition, hTERT extends the life span of cultured cells far beyond normal senescence without causing neoplastic transformation
12135889Cells expressing hTERT have been in continuous culture for >10 mo, whereas the control culture senesced after approximately 2 mo
12135889Myometrial cells immortalized with hTERT retained markers of differentiation that are observed in primary cultures of smooth muscle cells
12122013Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts
12122013Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan
12122013Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability
12122013By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length
12122013The shorter telomere lengths and the extent of karyotypic abnormalities are both functions of hTERT expression level
12101184Stable introduction of hTERT, the catalytic protein component of telomerase, into MCF-7 cells caused an increase in telomerase activity and telomere length
12083799In all cell lines, BPV E2-mediated inhibition of HPV E6/E7 expression caused a dramatic suppression of cell growth, being preceded by the activation of the p53-Rb growth-inhibitory pathway, and a decrease in hTERT mRNA expression and telomerase activity
12036938Ectopic expression of a COOH-terminal fragment of the human telomerase reverse transcriptase leads to telomere dysfunction and reduction of growth and tumorigenicity in HeLa cells
12036938The COOH-terminus of telomerase reverse transcriptase (hTERT) has been shown to participatein the nuclear translocation of TERT
12036938Here, we constructed plasmids expressing the COOH-terminal M(r) 27,000 polypeptide of hTERT (hTERTC27) withthe telomerase RNA-binding domains and the reverse transcriptase domains deleted
12036938Results from this study revealed an important function for the COOH terminus of hTERT in maintaining the integrity of telomere structure and chromosome ends, as well as in cell senescence and apoptosis
12018844The level of human telomerase reverse transcriptase (hTERT) mRNA was lower in MKN/ADR cell line than in MKN-45 cell line
11925625Expressions of subunits of telomerase, hTR and hTERT, were assessed by RT-PCR
11925625From the 12th to the 16th passages, many senescent and apoptotic cells appeared, and the telomere length sharply shortened from 23kb to 17kb without expression of hTERT and telomerase activity
11850774The specificity of the promoter for the telomerase catalytic gene and the antigenicity of the protein product, hTERT, provide additional strategies for killing telomerase-positive tumor cells
11718848We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain
11718848We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage
11718848Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide
11718848Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents
11718848Our data therefore suggest roles for TERT in modulating such cell deaths
11714633To explore the role of telomerase and telomere length in induced senescence, we expressed an exogenous hTERT gene, which encodes the catalytic subunit of telomerase, to generate stable HeLa cell clones with elevated telomerase activity and extended telomeres
11714633Cells carrying the hTERT gene and control cells displayed identical responses to E2 expression
11679409To clarify the association between aging and loss of endothelial function, young human aortic endothelial cells (HAECs), senescent HAECs transfected with control vector, and immortalized HAECs containing human telomerase reverse transcriptase (hTERT) were compared for expression of endothelial nitric oxide synthase (eNOS) and production of NO
11679409In all cells, shear stress induced a greater increase in the expression of eNOS protein with the final result being higher levels in hTERT compared with senescent cells
11679409Exposure of TNF-alpha resulted in a 2-fold increase in monocyte adhesion in senescent cells, whereas this effect was reduced in cells transfected with hTERT
11679409Stable expression of hTERT results in endothelial cells with a younger phenotype with greater amount of eNOS and NO activity
11602203These changes appear to be important for replicative senescence because they do not occur in melanocytes that overexpress the catalytic subunit of the enzyme telomerase (hTERT), or in melanomas, which are tumors that originate from melanocytes or melanoblasts
11602203In contrast to unmodified melanocytes, hTERT overexpressing (telomerized) melanocytes displayed telomerase activity, stable telomere lengths and an extended replicative life span
11557273To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase
11557273The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity
11531263Telomerase reverse transcriptase and telomeric-repeat binding factor protein 1 as regulators of telomerase activity in pancreatic cancer cells
11531263Recently, a number of relevant genes have been cloned, including these encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1)
11531263Of the three telomerase components, only hTERT mRNA expression showed parallel changes
11531263In this study, our results demonstrate that not only hTERT but also TRF1 are important regulator of telomerase activity
11481865They included those for human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein 1 (TEP1)
11481865Our results suggest that not only hTERT but also TRF1 and 2 are important regulators of telomerase activity
11468156Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential
11468156Recent studies have shown that the replicative life span of various primary human cells can be prolonged by induced expression of the telomerase reverse transcriptase (hTERT) gene
11468156To test whether introduction of hTERT can extend the life span of primary human T lymphocytes, naive CD8(+) T lymphocytes were transfected with retroviral vectors containing the hTERT gene
11468156These results indicate that ectopic hTERT gene expression is capable of extending the replicative life span of primary human CD8(+) cytotoxic T lymphocytes
11431323Using this model, we show that expression of human telomerase catalytic component (hTERT), but not E7-mediated inactivation of pRb or E6/E7-mediated inactivation of p53/pRb, was sufficient to initiate the tumorigenic process by circumventing cellular senescence in astrocytes
11376932Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)
11376932Recent interest in the regulation of telomerase, the enzyme that maintains chromosomal termini, has lead to the discovery and characterization of the catalytic subunit of telomerase, hTERT
11376932Many studies have suggested that the transcription of hTERT represents the rate-limiting step in telomerase expression and key roles for hTERT have been implied in cellular aging, immortalization, and transformation
11376932Before the characterization of the promoter of hTERT in 1999, regulatory mechanisms suggested for this gene were limited to speculation
11376932The successful cloning and characterization of the hTERT 5' gene regulatory region has enabled its formal investigation and analysis of potential mechanisms controlling hTERT expression
11376932Although these studies have provided important information about hTERT gene regulation, there has been some confusion regarding the nucleotide boundaries of this region, the location, number, and importance of various transcription factor binding motifs, and the results of promoter activity assays
11376932We feel that this uncertainty, combined with the sheer volume of recent publications on hTERT regulation, calls for consolidation and review
11376932In this analysis we examine recent advances in the regulation of the hTERT gene and attempt to resolve discrepancies resulting from the nearly simultaneous nature of publications in this fast-moving area
11376932Additionally, we aim to summarize the extant knowledge of hTERT gene regulation and its role in important biological processes such as cancer and aging
11344338METHODS: Primary cultures of cells derived from mouse corneal stroma were transfected with a human telomerase reverse transcriptase (hTERT) expression construct to maximize chances of cellular immortalization
11344338Expression of hTERT may contribute to immortalization of the MK/T-1 cells by a mechanism other than increases in RTL
11322991The catalytic subunit of telomerase (TERT) remains at relatively high levels during the process of neuronal differentiation and then decreases sharply during the period when synapses form and programmed cell death occurs
11322991TERT promotes survival of developing brain neurons
11322991Suppression of telomerase activity and TERT expression promotes apoptosis of neurons, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade TERT may suppress DNA damage and/or apoptotic signals activated by damaged DNA
11322991Recent studies of the transcriptional regulation of the TERT gene suggest that this enzyme may mediate the cell survival-promoting actions of diverse signals including estrogen, cytokines and neurotrophic factors
11322991The elucidation of the functions of telomerase activity and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and promoting recovery of function in various neurodegenerative conditions
11191109The telomerase catalytic subunit (hTERT) is an essential component of the holoenzyme complex that adds telomeric repeats to the ends of human chromosomes
11191109Available evidence suggests that regulation of telomerase activity primarily depends on transcriptional control of hTERT
11191109However, several human tissues as well as some normal cell strains have been shown to express low levels of hTERT mRNA even though they lack telomerase activity
11191109We have previously identified six splice variants of hTERT, including a "deletion" variant (hTERTalpha) that is missing conserved residues from the catalytic core of the protein
11191109These results suggest a possible role for hTERT splice variants in the regulation of telomerase activity
11179492The hTERT expression level was strongly associated with telomerase activity (P=0
11163759To determine the role of telomerase in regulating apoptosis, telomerase negative human embryo lung fibroblasts were transfected with the hTERT gene
11123427Role of human telomerase reverse transcriptase and telomeric-repeat binding factor proteins 1 and 2 in human hematopoietic cells
11123427Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1)
11123427In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected
11123427Of the three telomerase components, only hTERT mRNA expression showed changes paralleling telomerase activity, becoming undetectable with differentiation
10963125The constituents of telomerase complex have recently been identified, and human telomerase reverse transcriptase (hTERT) has been found to be responsible for the enzymatic activity of telomerase
10963125Detection of hTERT mRNA may therefore be useful for the screening and diagnosis of cancers
10963125The mechanisms regulating hTERT expression have been extensively analyzed, and transcriptional regulation of hTERT has been found to be essential for hTERT expression, in which several nuclear factors including c-Myc play crucial roles
10896778The lifespan of human fibroblasts and other primary cell strains can be extended by expression of the telomerase catalytic subunit (hTERT)
10856888The senescent phenotype was not prevented by retroviral transduction of the hTERT gene, although telomerase activity was induced
10744686Human fibroblasts expressing the catalytic component of human telomerase (hTERT) have been followed for 250-400 population doublings
10744686Cells with subsenescent telomere lengths proliferated for an additional 20 doublings after inhibiting telomerase activity with a dominant-negative hTERT mutant
10648922The majority of human cancers and tumor cell lines produce telomerase, a ribonucleoprotein with two components required for core enzyme activity: telomerase RNA (TR) and a telomerase reverse transcriptase protein (TERT)
10648922While TR of telomerase is present in almost all human cells, human TERT (hTERT) was found rate limiting for telomerase activity
10648922Ectopic expression of hTERT in otherwise mortal human cells induced efficient elongation of telomeres and permanent cell growth
10648922One oncogene that might activate TERT in the natural context is c-myc
10606235This activation accompanied up-regulation of the telomerase catalytic subunit, hTERT mRNA
10606235Gel shift assays revealed that the imperfect palindromic estrogen-responsive element in the hTERT promoter specifically binds to ER
10606235Transient expression assays using luciferase reporter plasmids containing various fragments of hTERT promoter showed that this imperfect palindromic estrogen-responsive element is responsible for transcriptional activation by ligand-activated ER
10606235We also found that estrogen activates c-Myc expression in MCF-7 cells and that E-boxes in the hTERT promoter that bind c-Myc/Max play additional roles in estrogen-induced transactivation of hTERT
10606235Estrogen thus activates telomerase via direct and indirect effects on the hTERT promoter
10082664When A549 cells were treated with TGF-beta, cell growth was not completely arrested, but the activity of telomerase was down regulated via transcriptional repression of telomerase reverse transcriptase, which led to a shortening of the telomere during long-term culture and finally resulted in replicative senescence
9916803As telomerase expression is a hallmark of cancer, we investigated the long-term effects of forced expression of human telomerase catalytic component (hTERT) in normal human fibroblasts
9751630Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts
9751630To investigate possible mechanisms of regulation, we examined telomerase activity and the expression of the human telomerase RNA subunit and the human telomerase reverse transcriptase protein (hTERT) during human fetal heart, liver, and kidney development
9751630However, although telomerase activity in the kidney is suppressed after the 15th gestational week, the hTERT transcript can be detected until at least the 21st week
9751630Reverse transcription-PCR using primers within the reverse transcriptase domain of hTERT show the presence of multiple alternately spliced transcripts in these tissues, corresponding to full-length message as well as spliced messages with critical reverse transcriptase motifs deleted
9751630Of note, telomerase activity in the kidney is only present at those gestational ages when full-length hTERT message is expressed (until approximately week 15), with spliced transcripts continuing to be expressed at later stages of development
9751630The tissue-specific and gestational-age dependent expression of hTERT mRNA seen in human development suggests the presence of at least two regulatory mechanisms controlling the activity of telomerase: transcriptional control of the hTERT gene and alternate splicing of hTERT transcripts
9655250Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence
9655250These results suggest that a senescence-inducing gene on chromosome 3 controls hEST2/hTRT gene expression either directly or indirectly and support the notion that hEST2/hTRT is the major determinant of telomerase enzymatic activity in human cells
9626480Levels of telomerase subunit mRNA (hEST2) were comparable among cell lines and tissues with different p53 status
9501072In yeast, the EST2 gene product, the catalytic subunit of telomerase, is essential for telomere maintenance in vivo [12-14]
9501072The recent cloning of the cDNA encoding the catalytic subunit of human telomerase (hTERT) [15,16] makes it possible to test the telomere hypothesis
9501072In this study, we expressed hTERT in normal human diploid fibroblasts, which lack telomerase activity, to determine whether telomerase activity could be reconstituted leading to extension of replicative life span
9501072Our results show that retroviral-mediated expression of hTERT resulted in functional telomerase activity in normal aging human cells
9501064Expression of the human telomerase subunit, hTERT, in primary cells now shows that these cells bypass senescence
9454332To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit
9398860Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT
9398860More recently, the human telomerase reverse transcriptase (hTRT; refs 15, 16), which is homologous to the reverse transcriptase (RT)-like proteins associated with the Euplotes aediculatus (Ea_p123), Saccharomyces cerevisiae (Est2p) and Schizosaccharomyces pombe (5pTrt1) telomerases, has been reported to be a telomerase protein subunit
9398860We now report that in vitro transcription and translation of hTRT when co-synthesized or mixed with hTR reconstitutes telomerase activity that exhibits enzymatic properties like those of the native enzyme
9398860Single amino-acid changes in conserved telomerase-specific and RT motifs reduce or abolish activity, providing direct evidence that hTRT is the catalytic protein component of telomerase
9398860Normal human diploid cells transiently expressing hTRT possessed telomerase activity, demonstrating that hTRT is the limiting component necessary for restoration of telomerase activity in these cells
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