HCSGD entry for AKT1
1. General information
| Official gene symbol | AKT1 |
|---|---|
| Entrez ID | 207 |
| Gene full name | v-akt murine thymoma viral oncogene homolog 1 |
| Other gene symbols | AKT CWS6 PKB PKB-ALPHA PRKBA RAC RAC-ALPHA |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000060 | Protein import into nucleus, translocation | IMP | biological_process |
| GO:0001649 | Osteoblast differentiation | IEA | biological_process |
| GO:0001893 | Maternal placenta development | IEA | biological_process |
| GO:0001934 | Positive regulation of protein phosphorylation | IDA | biological_process |
| GO:0001938 | Positive regulation of endothelial cell proliferation | IMP | biological_process |
| GO:0004672 | Protein kinase activity | IEA TAS | molecular_function |
| GO:0004674 | Protein serine/threonine kinase activity | IDA IEA TAS | molecular_function |
| GO:0005080 | Protein kinase C binding | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IC IDA IEA | molecular_function |
| GO:0005547 | Phosphatidylinositol-3,4,5-trisphosphate binding | IDA | molecular_function |
| GO:0005634 | Nucleus | IDA IEA TAS | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005737 | Cytoplasm | IDA ISS TAS | cellular_component |
| GO:0005819 | Spindle | IEA | cellular_component |
| GO:0005829 | Cytosol | IDA IEA TAS | cellular_component |
| GO:0005886 | Plasma membrane | IDA TAS | cellular_component |
| GO:0005978 | Glycogen biosynthetic process | IEA | biological_process |
| GO:0005979 | Regulation of glycogen biosynthetic process | IMP | biological_process |
| GO:0006006 | Glucose metabolic process | IEA | biological_process |
| GO:0006412 | Translation | IEA | biological_process |
| GO:0006417 | Regulation of translation | IEA | biological_process |
| GO:0006464 | Cellular protein modification process | TAS | biological_process |
| GO:0006468 | Protein phosphorylation | IDA | biological_process |
| GO:0006469 | Negative regulation of protein kinase activity | IEA IMP ISS | biological_process |
| GO:0006809 | Nitric oxide biosynthetic process | TAS | biological_process |
| GO:0006915 | Apoptotic process | TAS | biological_process |
| GO:0006924 | Activation-induced cell death of T cells | IMP | biological_process |
| GO:0006954 | Inflammatory response | IEA | biological_process |
| GO:0007165 | Signal transduction | TAS | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0007186 | G-protein coupled receptor signaling pathway | TAS | biological_process |
| GO:0007281 | Germ cell development | IEA | biological_process |
| GO:0007568 | Aging | IEA | biological_process |
| GO:0007596 | Blood coagulation | TAS | biological_process |
| GO:0008283 | Cell proliferation | TAS | biological_process |
| GO:0008286 | Insulin receptor signaling pathway | IMP | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0008637 | Apoptotic mitochondrial changes | IEA | biological_process |
| GO:0009408 | Response to heat | TAS | biological_process |
| GO:0010467 | Gene expression | TAS | biological_process |
| GO:0010507 | Negative regulation of autophagy | IMP | biological_process |
| GO:0010748 | Negative regulation of plasma membrane long-chain fatty acid transport | IMP | biological_process |
| GO:0010765 | Positive regulation of sodium ion transport | IEA | biological_process |
| GO:0010907 | Positive regulation of glucose metabolic process | IMP | biological_process |
| GO:0010951 | Negative regulation of endopeptidase activity | IMP | biological_process |
| GO:0010975 | Regulation of neuron projection development | IEA ISS | biological_process |
| GO:0015630 | Microtubule cytoskeleton | IDA | cellular_component |
| GO:0015758 | Glucose transport | IEA | biological_process |
| GO:0016070 | RNA metabolic process | TAS | biological_process |
| GO:0016071 | MRNA metabolic process | TAS | biological_process |
| GO:0016301 | Kinase activity | IDA | molecular_function |
| GO:0016310 | Phosphorylation | IDA | biological_process |
| GO:0016567 | Protein ubiquitination | IEA | biological_process |
| GO:0018105 | Peptidyl-serine phosphorylation | IDA IEA | biological_process |
| GO:0019899 | Enzyme binding | ISS | molecular_function |
| GO:0030030 | Cell projection organization | IEA | biological_process |
| GO:0030154 | Cell differentiation | TAS | biological_process |
| GO:0030163 | Protein catabolic process | IEA | biological_process |
| GO:0030168 | Platelet activation | TAS | biological_process |
| GO:0030212 | Hyaluronan metabolic process | IEA | biological_process |
| GO:0030235 | Nitric-oxide synthase regulator activity | IMP | molecular_function |
| GO:0030307 | Positive regulation of cell growth | IDA IEA | biological_process |
| GO:0030334 | Regulation of cell migration | IEA IMP TAS | biological_process |
| GO:0031018 | Endocrine pancreas development | TAS | biological_process |
| GO:0031295 | T cell costimulation | TAS | biological_process |
| GO:0031659 | Positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle | IDA | biological_process |
| GO:0031999 | Negative regulation of fatty acid beta-oxidation | IMP | biological_process |
| GO:0032094 | Response to food | IEA | biological_process |
| GO:0032270 | Positive regulation of cellular protein metabolic process | ISS | biological_process |
| GO:0032287 | Peripheral nervous system myelin maintenance | IEA | biological_process |
| GO:0032436 | Positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA | biological_process |
| GO:0032869 | Cellular response to insulin stimulus | IEA IMP ISS | biological_process |
| GO:0032880 | Regulation of protein localization | IEA | biological_process |
| GO:0033138 | Positive regulation of peptidyl-serine phosphorylation | IDA | biological_process |
| GO:0034405 | Response to fluid shear stress | IMP | biological_process |
| GO:0035556 | Intracellular signal transduction | IDA | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0042593 | Glucose homeostasis | IEA | biological_process |
| GO:0042640 | Anagen | IEA | biological_process |
| GO:0042802 | Identical protein binding | IPI | molecular_function |
| GO:0043065 | Positive regulation of apoptotic process | IEA | biological_process |
| GO:0043066 | Negative regulation of apoptotic process | IDA IEA | biological_process |
| GO:0043154 | Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process | IEA ISS | biological_process |
| GO:0043325 | Phosphatidylinositol-3,4-bisphosphate binding | IDA | molecular_function |
| GO:0043491 | Protein kinase B signaling | IEA | biological_process |
| GO:0043536 | Positive regulation of blood vessel endothelial cell migration | IDA | biological_process |
| GO:0044281 | Small molecule metabolic process | TAS | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045429 | Positive regulation of nitric oxide biosynthetic process | IMP | biological_process |
| GO:0045600 | Positive regulation of fat cell differentiation | IMP | biological_process |
| GO:0045725 | Positive regulation of glycogen biosynthetic process | IMP NAS | biological_process |
| GO:0045792 | Negative regulation of cell size | IEA | biological_process |
| GO:0045861 | Negative regulation of proteolysis | IMP | biological_process |
| GO:0045907 | Positive regulation of vasoconstriction | IEA | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IEA | biological_process |
| GO:0046209 | Nitric oxide metabolic process | TAS | biological_process |
| GO:0046326 | Positive regulation of glucose import | IMP | biological_process |
| GO:0046329 | Negative regulation of JNK cascade | IEA | biological_process |
| GO:0046777 | Protein autophosphorylation | TAS | biological_process |
| GO:0046889 | Positive regulation of lipid biosynthetic process | IMP | biological_process |
| GO:0048009 | Insulin-like growth factor receptor signaling pathway | IMP | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048015 | Phosphatidylinositol-mediated signaling | TAS | biological_process |
| GO:0050999 | Regulation of nitric-oxide synthase activity | TAS | biological_process |
| GO:0051000 | Positive regulation of nitric-oxide synthase activity | IMP | biological_process |
| GO:0051091 | Positive regulation of sequence-specific DNA binding transcription factor activity | IDA | biological_process |
| GO:0051146 | Striated muscle cell differentiation | IEA | biological_process |
| GO:0060644 | Mammary gland epithelial cell differentiation | TAS | biological_process |
| GO:0060709 | Glycogen cell differentiation involved in embryonic placenta development | IEA | biological_process |
| GO:0060716 | Labyrinthine layer blood vessel development | IEA | biological_process |
| GO:0070141 | Response to UV-A | IDA | biological_process |
| GO:0071260 | Cellular response to mechanical stimulus | IEA | biological_process |
| GO:0071364 | Cellular response to epidermal growth factor stimulus | IEA | biological_process |
| GO:0071456 | Cellular response to hypoxia | IEA | biological_process |
| GO:0071889 | 14-3-3 protein binding | IPI | molecular_function |
| GO:0090004 | Positive regulation of establishment of protein localization to plasma membrane | IMP | biological_process |
| GO:0090201 | Negative regulation of release of cytochrome c from mitochondria | IEA ISS | biological_process |
| GO:0097193 | Intrinsic apoptotic signaling pathway | TAS | biological_process |
| GO:0097194 | Execution phase of apoptosis | IEA | biological_process |
| GO:1900740 | Positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway | TAS | biological_process |
| GO:1901976 | Regulation of cell cycle checkpoint | TAS | biological_process |
| GO:1902176 | Negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress | NAS | biological_process |
| GO:2001240 | Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand | TAS | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.7019479123 | 0.1431807264 | 0.9999902473 | 0.7288879157 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.0033031774 |
| GSE13712_SHEAR | Up | 0.0220124807 |
| GSE13712_STATIC | Down | -0.1712380488 |
| GSE19018 | Up | 0.1217563242 |
| GSE19899_A1 | Down | -0.8623002851 |
| GSE19899_A2 | Up | 0.0788354091 |
| PubMed_21979375_A1 | Up | 0.3597812780 |
| PubMed_21979375_A2 | Up | 0.1252944125 |
| GSE35957 | Down | -0.7170960441 |
| GSE36640 | Down | -0.3700966536 |
| GSE54402 | Up | 0.3575882134 |
| GSE9593 | Down | -0.3528114187 |
| GSE43922 | Down | -0.1423491403 |
| GSE24585 | Down | -0.3244014157 |
| GSE37065 | Down | -0.1634293846 |
| GSE28863_A1 | Up | 0.0828591170 |
| GSE28863_A2 | Up | 0.0915255635 |
| GSE28863_A3 | Up | 0.2714628260 |
| GSE28863_A4 | Up | 0.0300529823 |
| GSE48662 | Up | 0.1378085727 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Adenosine triphosphate | DB00171 | NUTR00017 | EXPT00007 |
| Inositol 1,3,4,5-Tetrakisphosphate | DB01863 | EXPT01943 | DB03265 |
| N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine | DB07584 | - |
| 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine | DB07585 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-125b-5p | MIMAT0000423 | MIRT004363 | qRT-PCR//Western blot | Functional MTI | 18649363 |
| hsa-miR-185-5p | MIMAT0000455 | MIRT004701 | Flow//Immunoblot//Microarray//qRT-PCR | Functional MTI (Weak) | 19688090 |
| hsa-miR-149-3p | MIMAT0004609 | MIRT005355 | Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCR;Other | Functional MTI | 20623644 |
| hsa-miR-451a | MIMAT0001631 | MIRT005740 | qRT-PCR//Western blot | Functional MTI | 20816946 |
| hsa-miR-302a-3p | MIMAT0000684 | MIRT007171 | Luciferase reporter assay | Functional MTI | 23185040 |
| hsa-miR-302b-3p | MIMAT0000715 | MIRT007172 | Luciferase reporter assay | Functional MTI | 23185040 |
| hsa-miR-302c-3p | MIMAT0000717 | MIRT007173 | Luciferase reporter assay | Functional MTI | 23185040 |
| hsa-miR-302d-3p | MIMAT0000718 | MIRT007174 | Luciferase reporter assay | Functional MTI | 23185040 |
| hsa-miR-143-3p | MIMAT0000435 | MIRT007179 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 23104321 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT029530 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-miR-193b-3p | MIMAT0002819 | MIRT041236 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-185-5p | MIMAT0000455 | NA | hsa-miR-185 | 19688090 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 122 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27081703 | Mechanistically, we found that MARCKS maintained CAF activation through suppression of cellular senescence and activation of the AKT/Twist1 signaling |
| 27508009 | In conclusion, our data indicated that SRT1720 could protect against endothelial senescence and maintain cell function via Akt/eNOS/VEGF axis |
| 27349269 | All of these findings indicate that FOXA1 promotes cell senescence in EC by interaction with p16INK4a, possibly via the AKT pathway |
| 27206970 | Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways |
| 27206970 | The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation |
| 27206970 | Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence |
| 27206970 | Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis |
| 27009837 | Bmi-1 knockdown by Ad-Bmi-1i downregulated VEGF via inhibiting AKT activity |
| 26848154 | Mechanistically, we show that the ATM, Akt and mTORC1 phosphorylation cascade integrates signals from the DNA damage response (DDR) towards PGC-1beta-dependent mitochondrial biogenesis, contributing to aROS-mediated activation of the DDR and cell cycle arrest |
| 26763397 | It also activated the mammalian Ste20-like protein kinase 1 (MST1); however the serine/threonine kinase Akt was downregulated |
| 26763397 | They are inhibited by phosphorylation by Akt through external and internal stimuli |
| 26657292 | Excess ROS promoted oxidative inactivation of protein phosphatase PP2A which in turn led to disruption of normal negative feed-back control of AKT/cyclin D1 signaling in cells treated with long-term FR |
| 26635065 | The observed distribution of cells at G1 and S phases was associated with a significant increase in expression of p21 protein along with decreased levels of pAKT/AKT and pERK/ERK ratio (p < 0 |
| 26577046 | PR isoform-specific regulation of the FOXO1/p21 axis recapitulated in human primary ovarian tumor explants treated with progestin; loss of progestin sensitivity correlated with high AKT activity |
| 26511486 | Given that human prostate cancer arises from precancerous lesions such as high-grade prostatic intraepithelial neoplasia (HG-PIN), which frequently have lost phosphatase and tensin homolog (PTEN) tumor suppressor permitting phosphatidylinositol-3-OH kinase (PI3K)-protein kinase B (AKT) oncogenic signaling, we tested the efficacy of MSeA to inhibit HG-PIN progression in Pten prostate-specific knockout (KO) mice and assessed the mechanistic involvement of p53-mediated cellular senescence and of the androgen receptor (AR) |
| 26511486 | Mechanistically, the long-term MSeA treatment not only sustained P53-mediated senescence, but also markedly reduced AKT phosphorylation and AR abundance in the Pten KO prostate |
| 26511486 | Because p53 signaling is likely to be intact in HG-PIN compared with advanced prostate cancer, the selective superactivation of p53-mediated senescence by MSeA suggests a new paradigm of cancer chemoprevention by strengthening a cancer progression barrier through induction of irreversible senescence with additional suppression of AR and AKT oncogenic signaling |
| 26390028 | Moreover, 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 |
| 26360782 | Furthermore, BK treatment of H2O2-exposed cells leads to elevated phosphorylation of RB, AKT, and cyclin D1 compared with H2O2-treatment alone |
| 26250908 | The determination of the activation of receptors such as FGFR1, Met, and insulin growth factor 1 receptor beta indicated that the augmented FGFR1/AKT signaling was specifically involved in premature senescence in a HS-dependent manner |
| 26250908 | Thus, blockade of either FGFR1 or AKT prohibited p53 and p21 accumulation and cell fate switched from cellular senescence to apoptosis |
| 25989537 | Leptin and Neutrophil-Activating Peptide 2 Promote Mesenchymal Stem Cell Senescence Through Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway in Patients With Systemic Lupus Erythematosus |
| 25988874 | Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway |
| 25988874 | Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway |
| 25988874 | Additionally, AKT/TOR signaling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification |
| 25988874 | Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation |
| 25945449 | RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level |
| 25945449 | With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells |
| 25845638 | Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway |
| 25845638 | The expression of related proteins, including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western blot |
| 25845638 | The 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 |
| 25845638 | DISCUSSION: Ox-LDL induced senescence of EPCs via inhibition of telomerase activity, which was influenced by oxidative stress and the Akt/hTERT pathway |
| 25845638 | CONCLUSION: Treatment of EPCs with ASP remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT phosphorylation and inhibition of oxidative stress |
| 25797700 | We found VEGFR2 to activate phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT, resulting in inactivation of p21 in HCT116 cells |
| 25797700 | Inhibitors of VEGFR2 and AKT induced senescence in HCT116 cells |
| 25797700 | VEGFR2 interacts with phosphatidylinositol-4,5-bisphosphate-3-kinase and AKT to inactivate p21 |
| 25789082 | Coenzyme Q10 inhibits the aging of mesenchymal stem cells induced by D-galactose through Akt/mTOR signaling |
| 25789082 | However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group |
| 25789082 | These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling |
| 25777063 | The molecular mechanisms involve substrate competition of tau and beta-catenin for glycogen synthase kinase 3beta (GSK-3beta); activation of Akt; preservation of Bcl-2 and suppression of Bax, cytosolic cytochrome-c, and caspase-3 activity; and upregulation of unfolded protein response (UPR), i |
| 25739910 | In this review we discuss the evidence showing how oxidative stress induces accelerated ageing by upregulating the phosphatidylinositol-4,5-bisphosphate 3-kinase/AKT/mechanistic target of rapamycin signalling pathway resulting in depletion of stem cells, defective autophagy, reduced antioxidant responses and defective mitochondrial function thus generating further oxidative stress |
| 25693733 | Fucoidan also promoted the expression of cell cycle-associated proteins (cyclin E, Cdk2, cyclin D1, and Cdk4) in senescent ECFCs, significantly reversed cellular senescence, and increased the proliferation of ECFCs via the FAK, Akt, and ERK signaling pathways |
| 25655189 | We further revealed AKT signaling as a potential miR-143 target, and an induction of miR-143 expression by MEF2A via KLF2 |
| 25587030 | Without affecting Akt phosphorylation, PMA increased phosphorylation of S6K (T389) and S6 (S240/244), and that was completely prevented by rapamycin |
| 25568097 | Mechanistic target of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with those from younger mice associated with the increased expression of the histone variant protein, MH2A, a marker for aging and potentially for senescence |
| 25543088 | We found an inverse regulation of MYBBP1A and AKT phosphorylation (pAKT(Ser473)), which was characteristic for the pre-senescent state after etoposide administration in vitro |
| 25504754 | Examination of the activities of the kinases downstream of EGFR revealed that the RAF-MEK-ERK signaling pathway was remarkably inhibited, whereas AKT phosphorylation was not altered |
| 25481090 | Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells |
| 25407160 | In addition, TUDCA increased differentiation of CD34(+) HSCs into EPC lineage cells via Akt activation |
| 25407160 | EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation |
| 25388834 | Our data showed that both eNOS and Akt phosphorylation, VEGF expression and nitric oxide production were significantly decreased, RMVECs ageing and apoptosis increased after ox-LDL induction for 24 hrs, all of which were effectively reversed by ciglitazone pre-treatment |
| 25377220 | Phosphorylation of eNOS at Ser1177 and Akt at Ser473 was 63% and 80% lower in aged cells, respectively, whereas phosphorylation of the eNOS inhibition site (Thr495) increased by 6 |
| 25346044 | Although PINCH-2 expression of survival pathway-related proteins (Akt and phospho-Akt) did not change upon suppression of PINCH-2 expression, cell migration-related proteins [matrix-metalloproteinase (MMP)-9 and -11] were upregulated through autocrine and paracrine activation |
| 25344604 | E2F1 attenuates FOXO3-mediated expression of MnSOD and Catalase without affecting FOXO3 protein stability, subcellular localization, or phosphorylation by Akt |
| 25263463 | Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells |
| 25203674 | Using inhibitors of the non-receptor tyrosine kinase Src or Akt, known interaction partners of AR, reduced the level of androgen-induced cellular senescence suggesting a partly non-genomic pathway to induce cellular senescence by AA |
| 25203674 | Using PP2 (4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) pyrimidine or Akt inhibitors, inhibitors of the nonreceptor tyrosine kinase Src or Akt, known interaction partners of AR, reduced the level of androgen-induced cellular senescence, suggesting a partly nongenomic pathway to induce cellular senescence by AA |
| 25184156 | The antiproliferative and apoptotic effects of sirtinol, a sirtuin inhibitor on human lung cancer cells by modulating Akt/beta-catenin-Foxo3a axis |
| 25184156 | Interestingly, the levels of phosphorylated Akt and beta-catenin were significantly downregulated with treating the apoptotic inducing doses |
| 25078983 | The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot |
| 24917460 | When Mv1Lu cells were exposed to TGF-beta1, PKCdelta phosphorylation simultaneously increased with GSK3 phosphorylation, and then AKT and ERK were phosphorylated |
| 24917460 | AKT phosphorylation and Smad signaling were independent of GSK3 phosphorylation, but ERK phosphorylation was downstream of GSK3 inactivation |
| 24813621 | Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways |
| 24801508 | This latter event, together with enhanced IKKbeta signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phosphorylation of Akt and cAMP response element-binding protein |
| 24713059 | These analyses suggest a role for Akt, nuclear factor-kappaB (NF-kappaB), heat shock protein 90 (HSP90), p70/p80 autoantigen, 14-3-3 proteins, and dynein in telomere functions |
| 24704832 | Nuclear PRAS40 couples the Akt/mTORC1 signaling axis to the RPL11-HDM2-p53 nucleolar stress response pathway |
| 24704832 | The proline-rich Akt substrate of 40 kDa (PRAS40) has recently been identified as a binding partner and inhibitor of the mechanistic (formerly referred to as mammalian) target of rapamycin complex 1 (mTORC1) |
| 24491556 | Treatment with FGF-2 rapidly induced activation of AKT and later induced ERK activation |
| 24491556 | Taken together, depletion of growth factors during serial passage could induce autophagy, senescence and down-regulation of stemness (proliferation via FGF-2/-4 and differentiation via HGF) through suppression of AKT and ERK signaling |
| 24476133 | We propose that AKT inhibition results in a transient regulation of specific mechanisms that ultimately drive cells into cellular senescence or cell death |
| 24476133 | In this study, we investigated specific mechanisms of AKT inhibition that resulted in senescence |
| 24476133 | We observed that administration of MK-2206, an allosteric AKT inhibitor, increased levels of reactive oxygen species, up-regulated the microRNA miR-182 and several senescence-associated genes (including p16, p53, p21, and beta-galactosidase), and drove leiomyoma cells into stress-induced premature senescence (SIPS) |
| 24476133 | This study provides a conceivable molecular mechanism of SIPS by AKT inhibition in fibroids |
| 24463355 | Attenuated AKT/PKB phosphorylation in response to PRKD2 silencing was a common observation made in p53(wt) and p53(mut) GBM cells |
| 24274936 | Macrophage migration inhibitory factor regulates AKT signaling in hypoxic culture to modulate senescence of human mesenchymal stem cells |
| 24274936 | The hypoxic condition also delayed cellular senescence of hMSCs, increased activation of AKT signaling, and upregulated both intra- and extracellular levels of macrophage migration inhibitory factor (MIF) compared to the normoxic condition |
| 24274936 | On the other hand, upregulated intra- and extracellular levels of MIF by stable MIF overexpression in normoxic culture increased the activation of AKT while decreasing mRNA expression of senescence-associated markers and increasing expression of potency-associated markers |
| 24274936 | Taken together, our findings suggest that hMSCs in hypoxic culture produce endogenous MIF to activate AKT signaling to delay the progression of cellular senescence |
| 24265816 | The sensitivity of glioblastoma cells to TMZ is interfered by many factors, such as the expression of O-6-methylguanine-DNA methyltransferase (MGMT) and activation of AKT signaling |
| 24265816 | NTN4 partially inhibited TMZ induced cell senescence and rescued AKT from dephosphorylation in U251MG cells, a cell line bearing decent levels of ITGB4 |
| 24265816 | However, addition of exogenous NTN4 displayed no significant effect on TMZ induced senescence rescue or AKT activation in U87MG cells, which expressed ITGB4 at low levels |
| 24265816 | These data suggest that NTN4 protects glioblastoma cells from TMZ induced senescence, probably via rescuing TMZ triggered ITGB4 dependent AKT dephosphorylation |
| 24265816 | This suggests that interfering the interaction between NTN4 and ITGB4 or concomitant use of the inhibitors of the AKT pathway may improve the therapeutic efficiency of TMZ |
| 24165795 | In vitro, T cells from patients exhibited increased phosphorylation of the kinase Akt and hyperactivation of the metabolic checkpoint kinase mTOR, enhanced glucose uptake and terminal effector differentiation |
| 23941874 | Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes |
| 23891756 | Our study further revealed that the inhibitory effects of metformin on DNA damage accumulation may be due to the down-regulation of age-related and oxidative stress-induced AKT activity |
| 23870914 | The debarked stems and green leaf extracts reduced Akt levels in Huh-7 cells, indicating that D |
| 23870914 | This, together with the inhibition of Akt or ERK signalling, resulted in suppression of Huh-7 cell proliferation |
| 23807740 | Expression profiles of certain relevant genes and proteins like p53, Akt, Bcl-2, Bax, cytochrome c and caspase 3 also provided evidence of ROS mediated p53 up-regulation and further boost in Bax expression and followed by cytochrome c release and activation of caspase 3 |
| 23523798 | CKIIalpha knock-down or CKII inhibitor treatment strikingly increased phosphorylation of mTOR, p70S6K, an mTOR substrate, and AKT, whereas CKIIalpha overexpression reduced this phosphorylation event |
| 23518504 | Caloric restriction or inactivation of the AKT homolog Sch9p inhibits senescence and death in stationary phase cells caused by the DNA replication inhibitor hydroxyurea or by inactivation of the DNA replication and repair proteins Sgs1p or Rad27p |
| 23336586 | We found that NO production and phosphorylation of AKT, ERK, and endothelial NO synthase (eNOS) were elevated by ICA in HUVECs |
| 24579735 | Recent studies suggest that oncogenic pathways, such as the insulin-like growth factor-1 (IGF-I), Ras, and Akt/PKB, can contribute to both aging and cancer not only by promoting growth and preventing apoptosis, but also by promoting DNA damage and genomic instability |
| 23184984 | CD158d initiates signaling through DNA-PKcs, Akt, and NF-kappaB for a proinflammatory and proangiogenic response |
| 23145129 | These elevations in Ras activity were associated with activation of downstream signaling including activation of ERK, AKT and mTOR |
| 22915839 | Sustained activation of survival (Akt) and proliferative (ERK1/2) kinases fosters robustness of cells |
| 22904099 | Compared with young EC, senescent cells displayed increased expression of senescence-associated beta-galactosidase, nitric oxide synthase (eNOS), and AKT kinase, and secreted increased amounts of growth factors (VEGF, TGF-beta), cytokines (IL-6, IL-8, MCP-1), adhesion molecules (sICAM-1), and matrix proteins (fibronectin) |
| 22548801 | Phenylbutyric acid induces the cellular senescence through an Akt/p21(WAF1) signaling pathway |
| 22548801 | In addition, we found that treatment with PBA activates Akt, which results in p21(WAF1) induction |
| 22548801 | Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt |
| 22548801 | This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence |
| 22548801 | Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21(WAF1) pathway by PERK inhibition |
| 22418434 | Consistent with this, insulin signaling was enhanced in the soleus muscle of MNUAK1KO mice, as evidenced by increased phosphorylation of IRS1 Tyr-608, AKT Thr-308, and TBC1D4 Thr-649 |
| 22302986 | We have shown that fibroblasts deficient in the Rac exchange factor Tiam1 promote invasion and metastasis of associated epithelial tumor cells |
| 22253608 | Insulin signaling to Akt was attenuated in livers of CPEB-deficient mice, suggesting that they might be defective in regulating glucose homeostasis |
| 22160218 | In terms of molecular mechanism, knockdown of DEPDC6/DEPTOR expression in HuH-7 cells caused S6K and 4E-BP activation, but suppressed Akt |
| 22160218 | Overexpression of DEPDC6/DEPTOR activated Akt and increased survival of HCC cells |
| 21909130 | AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: implications for targeting mTOR during malignancy |
| 21909130 | Furthermore, our data imply that chronic activation of AKT signalling provides selective pressure for the loss of p53 function, consistent with observations that PTEN or PIK3CA mutations are significantly associated with p53 mutation in a number of human tumour types |
| 21881167 | Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells |
| 21881167 | To determine if active Akt-1 and Raf-1 can influence drug-induced senescence, we stably introduced activated DeltaAkt-1(CA) and DeltaRaf-1(CA) into drug-sensitive and doxorubicin-resistant cells |
| 21881167 | Constitutive activation of the Akt pathway significantly decreased drug-induced senescence in response to doxorubicin but not tamoxifen in MCF-7 cells |
| 21881167 | However, constitutive Akt-1 activation in drug-resistant cells containing high levels of active ERK completely escaped cellular senescence induced by doxorubicin and tamoxifen |
| 21730299 | Cellular senescence impaired angiogenic functions in ECs without attenuating the mitogen-activated protein kinase or Akt signaling, and vascular endothelial growth factor receptor 2 or Tie-2 expressions |
| 21622994 | Uremia decreased hypoxia-inducible factor-1alpha, VEGF and VEGFR1 expression under hypoxia and Akt phosphorylation in both basal and VEGF-stimulated states |
| 21486281 | The activity of Akt, a pro-survival kinase, was increased by atorvastatin in LG-cultured but not in HG-cultured CACs, whereas NCX 547 increased Akt activity in both conditions |
| 21439968 | The activities of eNOS, Akt and concentrations of nitric oxide (NO) were also determined |
| 21439968 | Administration of globular adiponectin at physiological concentrations promoted EPC migration and tube formation, and dose-dependently upregulated phosphorylation of eNOS, Akt and augmented NO production |
| 21418510 | We observed a sharp decrease in Akt activity during this process, suggesting a possible role of the PI3K-Akt pathway in hSKP maintenance in vitro |
| 21390332 | The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR |
| 21390332 | Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling |
| 21324896 | The impaired p85alpha(-/-) osteoblast differentiation was associated with increased activation of Akt and MAPK |
| 21286718 | Irinotecan increases phosphorylation of EGFR, MAPK, and AKT and decreases the expression of P27(Kip1), which could be all abrogated by its combination with cetuximab |
| 21256021 | Consistent with this, we show that oncogenic mutations in p110alpha (H1047R and E545K) partially evade this negative regulation, resulting in increased AKT activity in the population |
| 21084758 | These include components of the DNA repair system, the tumor suppressor pathway, the telomere maintenance system, the insulin/Akt pathway, and other metabolic pathways |
| 20938987 | CONCLUSION: Curcumin induces cellular stress responses in normal human skin fibroblasts through phosphatidylinositol 3-kinase/Akt pathway and redox signaling, supporting the view that curcumin-induced hormetic stimulation of cellular antioxidant defenses can be a useful approach toward anti-aging intervention |
| 20890302 | On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence |
| 20639198 | Oxidative stress induced senescence in endothelial cells through activation/phosphorylation of ATM by way of an Akt/p53/p21-mediated pathway |
| 20639198 | Collectively, our results show that ATM through an ATM/Akt/p53/p21-dependent signaling pathway mediates an instructive role in oxidative stress-induced endothelial dysfunction and premature senescence |
| 20398956 | Akt and eNOS activity was analyzed by western blot |
| 20398956 | Furthermore, high glucose induced a decrease in Akt and eNOS activity, and L-arginine prevented the decrease in activity |
| 20300111 | Jun(d/d) mouse embryonic fibroblasts (MEFs) exhibit early senescence, which can be rescued by EGF and HB-EGF stimulation, probably through activation of Akt signaling |
| 20174572 | Exploring the gain of function contribution of AKT to mammary tumorigenesis in mouse models |
| 20174572 | Elevated expression of AKT has been noted in a significant percentage of primary human breast cancers, mainly as a consequence of the PTEN/PI3K pathway deregulation |
| 20174572 | To investigate the mechanistic basis of the AKT gain of function-dependent mechanisms of breast tumorigenesis, we explored the phenotype induced by activated AKT transgenes in a quantitative manner |
| 20174572 | We generated several transgenic mice lines expressing different levels of constitutively active AKT in the mammary gland |
| 20174572 | We thoroughly analyzed the preneoplastic and neoplastic mammary lesions of these mice and correlated the process of tumorigenesis to AKT levels |
| 20174572 | Finally, our work also suggests that the cooperation observed between mutant p53 and activated AKT is due to AKT-induced acceleration of mutant p53-induced tumors |
| 20174572 | Finally, our work shows that levels of activated AKT are not essential in the induction of benign or premalignant tumors, or in the cooperation of AKT with other tumorigenic signal such as mutant p53, once AKT pathway is activated, the relative level of activity seems not to determine the phenotype |
| 20032052 | Prolactin exerts a prosurvival effect on human spermatozoa via mechanisms that involve the stimulation of Akt phosphorylation and suppression of caspase activation and capacitation |
| 20032052 | Western blot analyses indicated that the prosurvival effect of PRL on human spermatozoa involved the stimulation of Akt phosphorylation, whereas inhibitors of phosphatidylinositol-3-OH kinase and Akt negated this effect, as did the direct induction of sperm capacitation with cAMP analogues |
| 19951988 | WNT16B is a new marker of cellular senescence that regulates p53 activity and the phosphoinositide 3-kinase/AKT pathway |
| 21994573 | Finally, antiproliferative and apoptosis deficiencies involving TGF-beta, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation |
| 19841470 | Data demonstrate that 1) the toxic effects of epirubicin mainly occur through NAD(P)H oxidase activation; 2) the erbB2 overexpression induced by epirubicin is a redox-sensitive mechanism largely dependent on NAD(P)H oxidase; 3) the loss of erbB2-related functions caused by B10 determines marginal cellular changes in untreated cells, but causes massive death by apoptosis in cells previously exposed to a prosenescent dose of epirubicin, 4) dexrazoxane promotes survival pathways, as demonstrated by the activation of Akt and the PI3K-dependent erbB2 overexpression; and 5) it also prevents epirubicin-induced senescence and renders epirubicin-treated cells more resistant to treatment with B10 |
| 19782086 | In UT-7, carbamylated erythropoietin (C-darbe) induced phosphorylation of the anti-apoptotic Jak-2/Akt signal and, as opposed to recombinant human erythropoietin (darbe), did not produce a significant activation of cell proliferating signals |
| 19647222 | We report that knocking down the expression of inositol polyphosphate 4-phosphatase type II (INPP4B) in human epithelial cells, like knockdown of PTEN, resulted in enhanced Akt activation and anchorage-independent growth and enhanced overall motility |
| 19647222 | 5-triphosphate (PI(3,4,5)P(3)), suggesting that PI(3,4)P(2) and PI(3,4,5)P(3) may cooperate in Akt activation and cell transformation |
| 19499400 | To examine further the underlying mechanisms of these effects, we measured telomerase activity and the phosphorylation of Akt by Western blotting |
| 19219070 | Protein analyses showed a reduction in the amount and activation of Akt and increased levels of p27(Kip1) upon Sox5 expression that was dominant to PDGFB signaling and specific to Ink4a-/- cells |
| 19150958 | We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro |
| 18765664 | S1P-induced Akt and ERK1/2 activation were comparable between ECs of different in vitro ages; however, PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity was significantly elevated and Rac activation was inhibited in senescent ECs |
| 18765664 | Rac activation and senescent-associated impairments were restored in senescent ECs by the expression of dominant-negative PTEN and by knocking down S1P(2) receptors |
| 18672169 | Treatment with IGF-1 up-regulated myocardial telomerase activity >14-fold and increased the expression of phosphorylated Akt protein kinase and phosphorylated eNOS |
| 18583712 | Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt |
| 18583712 | When VEGFR-1 expression was blocked, VEGF constitutively activated Akt signals and thus induced endothelial cell senescence via a p53-dependent pathway |
| 18583712 | VEGFR-1(+/-) mice exhibited an increase of endothelial Akt activity and showed an impaired neovascularization in response to ischemia, and this impairment was ameliorated in VEGFR-1(+/-) Akt1(+/-) mice |
| 18577387 | We propose a stochastic model of p53 regulation, which is based on two feedback loops: the negative, coupling p53 with its immediate downregulator Mdm2, and the positive, which involves PTEN, PIP3 and Akt |
| 18498745 | Interestingly, while embryonic fibroblasts of Cul7-/- mice were found to accumulate IRS-1 and exhibit increased activation of IRS-1's downstream Akt and MEK/ERK pathways, these null cells grew poorly and displayed phenotypes reminiscent of those associated with oncogene-induced senescence |
| 18195103 | As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e |
| 17312453 | To get further insights into the underlying mechanisms of these effects, we measured telomerase activity and determined the phosphorylation of Akt by Western blotting |
| 17312453 | Taken together, the results indicated that Ginkgo biloba extract delayed the onset of EPC senescence, which may be related to activation of telomerase through the PI3k/Akt signaling pathway |
| 17234973 | IGF-1 increased telomerase activity, endothelial nitric oxide synthase expression, phosphorylation and activity in EPC in a phosphoinositide-3-kinase/Akt dependent manner |
| 17204661 | These include components of the DNA-repair system, the tumor suppressor pathway, the telomere maintenance system, the insulin/Akt pathway, and other metabolic pathways |
| 16813094 | Constitutive activation of Akt also induces vascular cell senescence |
| 16813094 | This novel role of Akt in regulating the cellular lifespan may contribute to various human diseases including atherosclerosis and diabetes mellitus |
| 16798746 | Raloxifene also induced the phosphorylation of Akt, and pretreatment with a phosphatidylinositol 3-kinase inhibitor, LY294002, significantly attenuated the raloxifene-induced telomerase activity |
| 16798746 | These 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 |
| 16600555 | By use of conditioned medium, we found a growth promoting impact of fibroblasts compared with control medium from epithelial cells associated with activation of ERK1/2, Akt, p70S6K, and EGF receptor |
| 16455826 | Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated |
| 16455826 | Phosphorylation of Akt was detected by Western blotting |
| 16455826 | A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours |
| 16455826 | Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation |
| 16283872 | Specifically, aged HDFs showed decreased cell viability, decreased phosphorylation (activation) of pro-survival kinases (Akt and ERK 1/2), and increased entrance into a senescent state when compared with their younger counterparts |
| 16170353 | However, tyrosine phosphorylation of the receptors for EGF and IGF-I and Akt/PKB activation were unaltered by Sirtinol treatment |
| 16093915 | Because the expression of TERT is regulated by the PI3-K/Akt pathway, we examined the effect of 17beta-estradiol on Akt activity in EPCs |
| 16093915 | Immunoblotting analysis revealed that 17beta-estradiol dose-dependently led to phosphorylation and, thus, to activation of Akt in EPCs |
| 15930307 | Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence |
| 15930307 | Because Akt pathway activation has been suggested to also block G2 arrest induced by DNA-damaging agents and because glioma cells frequently have high levels of Akt activation, we examined the contribution of the Akt pathway to methylating agent-induced G2 arrest and toxicity |
| 15930307 | U87MG human glioma cells containing an inducible Akt expression construct were incubated with inducing agent or vehicle, after which the cells were exposed to temozolomide and assayed for activation of the components of the G2 arrest pathway and survival |
| 15930307 | These results show that whereas Akt activation suppresses temozolomide-induced Chk2 activation and G2 arrest, the overriding effect is protection from temozolomide-induced cytotoxicity |
| 15930307 | The Akt pathway therefore represents a new target for the sensitization of gliomas to chemotherapeutic methylating agents such as temozolomide |
| 15741276 | The signaling pathway of insulin/insulin-like growth factor/phosphatidylinositol-3 kinase/Akt/forkhead transcription factors is known to control life span and senescence in organisms ranging from yeast to mice |
| 15098029 | Our results implicate activation of eIF-4E as a key event in oncogenic transformation by phosphoinositide-3 kinase and Akt |
| 15004530 | Reduction-of-function mutations in components of the insulin/insulin-like growth factor-1/Akt pathway have been shown to extend the lifespan in organisms ranging from yeast to mice |
| 15004530 | It has also been reported that activation of Akt induces proliferation and survival of mammalian cells, thereby promoting tumorigenesis |
| 15004530 | We have recently shown that Akt activity increases with cellular senescence and that inhibition of Akt extends the lifespan of primary cultured human endothelial cells |
| 15004530 | Constitutive activation of Akt promotes senescence-like arrest of cell growth via a p53/p21-dependent pathway, leading to endothelial dysfunction |
| 15004530 | This novel role of Akt in regulating the cellular lifespan may contribute to various human diseases including atherosclerosis and diabetes mellitus |
| 14726476 | Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation |
| 14713953 | Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway |
| 14713953 | The signaling pathway of insulin/insulin-like growth factor-1/phosphatidylinositol-3 kinase/Akt is known to regulate longevity as well as resistance to oxidative stress in the nematode Caenorhabditis elegans |
| 14713953 | Although reduction-of-function mutations in components of this pathway have been shown to extend the lifespan in organisms ranging from yeast to mice, activation of Akt has been reported to promote proliferation and survival of mammalian cells |
| 14713953 | Here we show that Akt activity increases along with cellular senescence and that inhibition of Akt extends the lifespan of primary cultured human endothelial cells |
| 14713953 | Constitutive activation of Akt promotes senescence-like arrest of cell growth via a p53/p21-dependent pathway, and inhibition of forkhead transcription factor FOXO3a by Akt is essential for this growth arrest to occur |
| 14713953 | These findings reveal a novel role of Akt in regulating the cellular lifespan and suggest that the mechanism of longevity is conserved in primary cultured human cells and that Akt-induced senescence may be involved in vascular pathophysiology |
| 12743603 | Specific molecular markers such as p21/WAF1, activated caspase-3 and activated Akt were associated with these death modes |
| 12743603 | The combination of doxorubicin and Q-VD-OPH caused an increased expression of p21/WAF1 and senescence -associated -beta-galactosidase activity, but did not alter Akt activation |
| 12470826 | Although total activity of ERK and Akt was similar in total cell lysates from early and late passage fibroblasts our data indicate that in senescent cells neither ERK nor Akt are able to phosphorylate efficiently their nuclear targets |
| 11751876 | We examined the role that the serine/threonine kinase Akt plays in collagenase expression during in vitro senescence of WI-38 normal human lung fibroblast cells |
| 11751876 | Dominant negative forms of Akt increase collagenase promoter activity in early passage WI-38 fibroblasts, whereas an active form of Akt suppresses steady state levels of collagenase mRNA in senescent WI-38 fibroblasts |
| 11480555 | Ceramide activation of protein phosphatases has been shown to promote inactivation of a number of pro-growth cellular regulators including the kinases PKC alpha and Akt, Bcl2 and the retinoblastoma protein |
| 11431323 | These alterations together, however, cooperated with ras pathway activation (initiated by expression of mutant H-Ras), but not with phosphatidylinositol 3-kinase pathway activation (initiated by expression of myristoylated Akt) or epidermal growth factor receptor activation, to allow for the formation of intracranial tumors strongly resembling p53/pRb pathway-deficient, telomerase-positive, ras-activated human grade III anaplastic astrocytomas |
| 10962000 | Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway |
| 10962000 | This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1) |
| 10593857 | Several proto-oncogenes and tumor suppressor genes have been implicated in the regulation of telomerase activity, both directly and indirectly; these include c-Myc, Bcl-2, p21(WAF1), Rb, p53, PKC, Akt/PKB, and protein phosphatase 2A |
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