HCSGD entry for RB1
1. General information
| Official gene symbol | RB1 |
|---|---|
| Entrez ID | 5925 |
| Gene full name | retinoblastoma 1 |
| Other gene symbols | OSRC RB p105-Rb pRb pp110 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
This gene isn't in PPI subnetwork.
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000075 | Cell cycle checkpoint | TAS | biological_process |
| GO:0000082 | G1/S transition of mitotic cell cycle | TAS | biological_process |
| GO:0000083 | Regulation of transcription involved in G1/S transition of mitotic cell cycle | TAS | biological_process |
| GO:0000278 | Mitotic cell cycle | TAS | biological_process |
| GO:0000785 | Chromatin | TAS | cellular_component |
| GO:0001047 | Core promoter binding | IDA | molecular_function |
| GO:0001102 | RNA polymerase II activating transcription factor binding | IEA | molecular_function |
| GO:0003674 | Molecular_function | ND | molecular_function |
| GO:0003677 | DNA binding | TAS | molecular_function |
| GO:0003700 | Sequence-specific DNA binding transcription factor activity | TAS | molecular_function |
| GO:0003713 | Transcription coactivator activity | NAS | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005575 | Cellular_component | ND | cellular_component |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005819 | Spindle | IEA | cellular_component |
| GO:0006338 | Chromatin remodeling | TAS | biological_process |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006469 | Negative regulation of protein kinase activity | IPI | biological_process |
| GO:0007050 | Cell cycle arrest | TAS | biological_process |
| GO:0007070 | Negative regulation of transcription from RNA polymerase II promoter during mitosis | TAS | biological_process |
| GO:0007093 | Mitotic cell cycle checkpoint | TAS | biological_process |
| GO:0007265 | Ras protein signal transduction | IEP | biological_process |
| GO:0007346 | Regulation of mitotic cell cycle | IMP | biological_process |
| GO:0008134 | Transcription factor binding | IPI | molecular_function |
| GO:0008150 | Biological_process | ND | biological_process |
| GO:0016032 | Viral process | IEA | biological_process |
| GO:0016514 | SWI/SNF complex | TAS | cellular_component |
| GO:0016605 | PML body | IDA | cellular_component |
| GO:0019900 | Kinase binding | IDA | molecular_function |
| GO:0030521 | Androgen receptor signaling pathway | NAS | biological_process |
| GO:0031134 | Sister chromatid biorientation | IMP | biological_process |
| GO:0031175 | Neuron projection development | IEA | biological_process |
| GO:0031625 | Ubiquitin protein ligase binding | IPI | molecular_function |
| GO:0034088 | Maintenance of mitotic sister chromatid cohesion | IMP | biological_process |
| GO:0034349 | Glial cell apoptotic process | IEA | biological_process |
| GO:0035189 | Rb-E2F complex | TAS | cellular_component |
| GO:0035914 | Skeletal muscle cell differentiation | IEA | biological_process |
| GO:0042551 | Neuron maturation | IEA | biological_process |
| GO:0042802 | Identical protein binding | IPI | molecular_function |
| GO:0043353 | Enucleate erythrocyte differentiation | IEA | biological_process |
| GO:0043433 | Negative regulation of sequence-specific DNA binding transcription factor activity | TAS | biological_process |
| GO:0043550 | Regulation of lipid kinase activity | IDA | biological_process |
| GO:0045445 | Myoblast differentiation | IMP | biological_process |
| GO:0045651 | Positive regulation of macrophage differentiation | IEA | biological_process |
| GO:0045842 | Positive regulation of mitotic metaphase/anaphase transition | IMP | biological_process |
| GO:0045879 | Negative regulation of smoothened signaling pathway | IEA | biological_process |
| GO:0045892 | Negative regulation of transcription, DNA-templated | IDA TAS | biological_process |
| GO:0045893 | Positive regulation of transcription, DNA-templated | NAS | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IEA | biological_process |
| GO:0048565 | Digestive tract development | IEA | biological_process |
| GO:0048667 | Cell morphogenesis involved in neuron differentiation | IEA | biological_process |
| GO:0050680 | Negative regulation of epithelial cell proliferation | IEA | biological_process |
| GO:0050681 | Androgen receptor binding | NAS | molecular_function |
| GO:0051146 | Striated muscle cell differentiation | IEA | biological_process |
| GO:0051219 | Phosphoprotein binding | IPI | molecular_function |
| GO:0051402 | Neuron apoptotic process | IEA | biological_process |
| GO:0071459 | Protein localization to chromosome, centromeric region | IMP | biological_process |
| GO:0071922 | Regulation of cohesin localization to chromatin | IMP | biological_process |
| GO:0071930 | Negative regulation of transcription involved in G1/S transition of mitotic cell cycle | IEA | biological_process |
| GO:0090230 | Regulation of centromere complex assembly | TAS | biological_process |
| GO:0097284 | Hepatocyte apoptotic process | IEA | biological_process |
| GO:2000134 | Negative regulation of G1/S transition of mitotic cell cycle | 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 |
|---|---|---|---|
| 0.9327900574 | 0.0515241214 | 0.9999902473 | 0.4267300314 |
- 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 | -0.2373834264 |
| GSE13712_SHEAR | Down | -0.0106554652 |
| GSE13712_STATIC | Down | -0.1844623652 |
| GSE19018 | Up | 0.0922978987 |
| GSE19899_A1 | Up | 0.0496517729 |
| GSE19899_A2 | Down | -0.5953432449 |
| PubMed_21979375_A1 | Up | 0.2567719868 |
| PubMed_21979375_A2 | Down | -0.4564283386 |
| GSE35957 | Up | 0.1549723699 |
| GSE36640 | Down | -0.5117242079 |
| GSE54402 | Down | -0.2264721531 |
| GSE9593 | Down | -0.1062816031 |
| GSE43922 | Down | -0.0492158268 |
| GSE24585 | Up | 0.3624071628 |
| GSE37065 | Up | 0.0236218230 |
| GSE28863_A1 | Down | -0.5166394918 |
| GSE28863_A2 | Down | -0.0564880156 |
| GSE28863_A3 | Down | -0.5810892030 |
| GSE28863_A4 | Up | 0.1145914390 |
| GSE48662 | Down | -0.1756242529 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Name | Drug | Accession number |
|---|---|---|
| Insulin Pork | DB00071 | BTD00031 | BIOD00031 |
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-192-5p | MIMAT0000222 | MIRT006435 | Immunoblot//Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 21511813 |
| hsa-miR-192-5p | MIMAT0000222 | MIRT006435 | Microarray | Functional MTI (Weak) | 19074876 |
| hsa-miR-212-3p | MIMAT0000269 | MIRT006504 | Luciferase reporter assay//Western blot//Reporter assay;Western blot;qRT-PCR | Functional MTI | 21329664 |
| hsa-miR-106a-5p | MIMAT0000103 | MIRT001840 | Microarray//immunohistochemistry | Functional MTI (Weak) | 19175831 |
| hsa-miR-106a-5p | MIMAT0000103 | MIRT001840 | Immunohistochemistry//Microarray//Western blot | Functional MTI | 20643754 |
| hsa-miR-106a-5p | MIMAT0000103 | MIRT001840 | Luciferase reporter assay//Microarray//Western blot//Reporter assay | Functional MTI | 16461460 |
| hsa-miR-106a-5p | MIMAT0000103 | MIRT001840 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 20889678 |
| hsa-miR-26a-5p | MIMAT0000082 | MIRT003213 | GFP reporter assay//Luciferase reporter assay//Western blot | Functional MTI | 20080666 |
| hsa-miR-26a-5p | MIMAT0000082 | MIRT003213 | Luciferase reporter assay//Microarray//qRT-PCR//Western blot | Functional MTI | 23108995 |
| hsa-miR-23b-3p | MIMAT0000418 | MIRT003425 | flow//Microarray | Functional MTI (Weak) | 20133741 |
| hsa-miR-335-5p | MIMAT0000765 | MIRT003587 | Luciferase reporter assay//Western blot | Functional MTI | 20713524 |
| hsa-miR-106b-5p | MIMAT0000680 | MIRT004664 | immunohistochemistry//Microarray | Functional MTI (Weak) | 19175831 |
| hsa-miR-106b-5p | MIMAT0000680 | MIRT004664 | Luciferase reporter assay | Functional MTI | 21283765 |
| hsa-miR-106b-5p | MIMAT0000680 | MIRT004664 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 21819631 |
| hsa-miR-106b-5p | MIMAT0000680 | MIRT004664 | Microarray | Functional MTI (Weak) | 17242205 |
| hsa-miR-675-5p | MIMAT0004284 | MIRT004749 | Luciferase reporter assay//qRT-PCR | Functional MTI | 19926638 |
| hsa-miR-17-5p | MIMAT0000070 | MIRT005850 | Luciferase reporter assay | Functional MTI | 21283765 |
| hsa-miR-20a-5p | MIMAT0000075 | MIRT005857 | Luciferase reporter assay | Functional MTI | 21283765 |
| hsa-miR-132-3p | MIMAT0000426 | MIRT006503 | Luciferase reporter assay//Western blot//Reporter assay;Western blot;qRT-PCR | Functional MTI | 21329664 |
| hsa-miR-130b-3p | MIMAT0000691 | MIRT020177 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-215-5p | MIMAT0000272 | MIRT024341 | Microarray | Functional MTI (Weak) | 19074876 |
| hsa-miR-93-5p | MIMAT0000093 | MIRT028033 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-21-5p | MIMAT0000076 | MIRT030738 | Microarray | Functional MTI (Weak) | 18591254 |
| hsa-miR-149-5p | MIMAT0000450 | MIRT045442 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-100-5p | MIMAT0000098 | MIRT048586 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-99a-5p | MIMAT0000097 | MIRT048653 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-106a-5p | MIMAT0000103 | NA | hsa-miR-106a | {activity assay} | {overexpression by mature miRNA transfection} | {luciferase} | 16461460 |
| hsa-miR-675-5p | MIMAT0004284 | 1 | hsa-miR-675 | {Western blot} | {endogenous} | 19926638 | |
| hsa-miR-106a-5p | MIMAT0000103 | 1 | hsa-miR-106a | {Western blot} | {overexpression by miRNA mimics tranfection} | 20889678 | |
| hsa-miR-192-5p | MIMAT0000222 | NA | hsa-miR-192 | {Western blot} | {overexpression by miRNA mimics tranfection} | 21511813 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 146 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26904954 | We show that miR-137 targets KDM4A mRNA during Ras-induced senescence and activates both p53 and retinoblastoma (pRb) tumor suppressor pathways |
| 26763147 | Expression of hCMV immediate early (IE) and early (E) proteins and senescence-associated proteins (pRb and Rb, p16(INK4), and p53) and production of reactive oxygen species (ROS) were assessed using standard laboratory assays |
| 26529363 | Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation |
| 26529363 | Importantly, we showed that knockdown of RAD21 resulted in the appearance of several senescent markers, including enhanced senescence-associated beta-galactosidase activity and heterochromatin focus formation, as well as elevated p21 protein levels and RB1 pathway activation |
| 26529363 | Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c-Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1-mediated transcriptional repression of E2F |
| 26465338 | These phenotypic changes were not accompanied by colonies forming in soft agar and a continuous decrease in the senescence-associated proteins p53 and pRB which act as a barrier to tumorigenesis |
| 26360782 | Bradykinin (BK) treatment decreased human EPC (hEPC) senescence and intracellular oxygen radical production, resulting in reduced retinoblastoma 1 (RB) RNA expression in H2O2-induced senescent hEPCs and a reversal of the B2R downregulation that is normally observed in senescent cells |
| 26215037 | Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1gamma, CDK4, cyclin D1, cyclin E, and p16 protein expressions |
| 26106036 | Furthermore, we uncover a novel form of haploinsufficiency-induced senescence (HIS) specific to epithelial cells, which is triggered by pRb pathway activation rather than p53 induction |
| 26106036 | HIS and telomere erosion in HMECs correlate with misregulation of SIRT1 leading to increased levels of acetylated pRb as well as acetylated H4K16 both globally and at telomeric regions |
| 26094870 | Simultaneous examination of p16(INK4A) expression, which predicts tumours that have bypassed cellular senescence, revealed that intermediate levels of p16(INK4A) correlate with an intact pRB pathway and improved survival |
| 26051603 | MATERIALS/METHODS: After pre-treatement with or without DHEA prior to LA treatment in human aortic endothelial cells (HAECs), the level of senescence was compared by senescence-associated acidic beta-galactosidase (SA-beta-Gal) staining and hyperphosphorylated pRB (ppRB) protein level |
| 25695870 | Although much is known about the key players in the implementation of senescence, including the pRb and p53 axes and the cyclin dependent kinase inhibitors p16(INK4a) and p21(CIP1), many details remain unresolved |
| 25695870 | At the permissive temperature, where pRb and p53 are functionally compromised by T-Ag, cyclin D-CDK4 complexes are disrupted by the high p16(INK4a) levels and reduced expression of p21(CIP1) |
| 25695870 | In cells arrested at the non-permissive temperature, p21(CIP1) promotes reassembly of cyclin D-CDK4 yet pRb is in a hypo-phosphorylated state, consistent with cell cycle arrest |
| 25684390 | We show that stable miR-433 expression in A2780 OC cells results in the induction of cellular senescence demonstrated by morphological changes, downregulation of phosphorylated retinoblastoma (p-Rb), and an increase in beta-galactosidase activity |
| 25684390 | Mechanistically, we demonstrate that downregulation of p-Rb is attributable to a miR-433-dependent downregulation of CDK6, establishing it as a novel miR-433 associated gene |
| 25675863 | The p16(INK4A)/pRb pathway and telomerase activity define a subgroup of Ph+ adult Acute Lymphoblastic Leukemia associated with inferior outcome |
| 25675863 | In BCR-ABL1+ ALLs, high CDK4 expression, phosphorylated pRb (p-pRb) and telomerase activity were significantly associated with a shorter disease-free survival (DFS) and event-free survival (EFS) |
| 25647436 | At 21% O2, DPCs showed flattened morphology and a significant reduction in mobility, population doubling, increased levels of reactive oxygen species and senescence-associated beta-Gal activity, and increased expression of p16(INK4a) and pRB |
| 25437011 | Activation of the Wnt pathway by treatment with Wnt3a-conditioned medium or glycogen synthase kinase 3beta inhibitors, such as SB-216763 and 6-bromoindirubin-3'-oxime, delays the progression of cellular senescence as shown by the decrease in the senescence effectors p53 and pRb, lowered senescence-associated beta-galactosidase activity, and increased telomerase activity |
| 24981831 | The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state |
| 24815188 | Interestingly, Mig-6 overexpression reduced retinoblastoma protein (pRb) phosphorylation at the inactivating Ser249/Thr252 sites |
| 24815188 | We also found that phosphorylation of these sites in pRb is increased in the presence of the B-Raf V600E oncogenic mutation |
| 24815188 | We further show that Mig-6 overexpression reduces B-Raf V600E mediated pRb inactivation and preserves pRb function |
| 24807532 | Furthermore, upregulation of p16(INK4a) was critical to the antitumor activity of HepG2 cells treated with fucoidan and was correlated with inhibition of Cdk4 and pRb and upregulation of p21 expression |
| 24747969 | Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2 |
| 24659628 | With aging, p85alpha, IGF-1 and B-myb muscle levels were lower while the expression of certain cell arrest proteins (p53, p16 and pRB) increased |
| 24626611 | Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated beta-galactosidase (SA-beta-Gal) activity, hypophosphorylation of pRb and p21 accumulation |
| 24587053 | In addition, TCDD exposure altered the expression of senescence marker proteins, such as p16, p21 and p-Rb, in both dose- and time-dependent manners |
| 24459734 | Two classical tumor suppressors, p53 and pRB, control cell cycle arrest associated with senescence |
| 24351540 | The pRB pathway plays a major role in senescence by directly repressing E2Fs and also by regulating chromatin at the promoters of E2F target genes using its LXCXE cleft-dependent interactions |
| 24351540 | In this study, we sought to investigate the mechanisms by which pRB stably silences E2F target gene transcription during cellular senescence |
| 24351540 | We report that in mouse embryonic fibroblasts, endogenous promyelocytic leukemia protein (PML) associates with E2F target genes in a pRB LXCXE-dependent manner during HrasV12-induced senescence |
| 24351540 | Furthermore, using a PML-IV-induced senescence model, we show that the pRB LXCXE binding cleft is essential for PML association with gene promoters, silencing of E2F target genes, and stable cell cycle exit |
| 24351540 | Binding assays show that pRB can interact with PML specifically during senescence, suggesting that signaling events in senescence regulate assembly of PML and pRB to establish heterochromatin and create a permanent cell cycle arrest |
| 24322375 | Analysis of expression levels of p53, p21(CIP1), p16(INK4a), p27(KIP1), pRb and E2F1 and genetic knockdown of p21(CIP1) demonstrated an important role of p21(CIP1) in RD-triggered cellular senescence |
| 24122992 | CONCLUSION: The absence of functional p16, pRB and p53 in DU145 suggests that Id4 could alter additional molecular pathways such as those involving E2F1 to promote senescence and increased sensitivity to doxorubicin-induced apoptosis |
| 23989658 | Combined treatment of MTOR inhibitor and radiation induce heterochromatin formation, an irreversible growth arrest and an increase of senescence-associated GLB1 (beta-galactosidase) activity, which appear to result from a constant activation of TP53 and a restoration in the activity of retinoblastoma 1 protein (RB1)-E2F1 |
| 23982736 | The expression of acetylated p53 at Lys382 (Ac-p53) and p21 was also increased, while phosphorylation of p53 at Ser15 (p-p53), p53, p16 and pRB was rarely altered after metformin treatment |
| 23438604 | BRG1 is a chromatin-remodeling factor that interacts with BRCA1 and pRB |
| 23438604 | This effect depends upon BRG1's chromatin-remodeling activity as well as the interaction between BRG1 and pRB |
| 23438604 | Indeed, the interaction between BRG1 and pRB is enhanced during senescence |
| 23438604 | Consistently, knockdown of pRB, p21(CIP1), and p16(INK4a), but not p53, suppressed SAHF formation induced by BRG1 |
| 23370776 | Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells |
| 23370776 | Cells lacking RB1 were prone to DNA damage |
| 22855034 | At the end of the 48-h culture, the following analyses were performed including determination of senescence-associated beta-galactosidase (SAbeta-Gal) activity, flow cytometry analysis of cell cycle, real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analyses of p16, Cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma (Rb) mRNA expression, and Western blotting analyses of p16, cyclin D1, CDK4 and phosphoretinoblastoma (pRb) protein expressions |
| 22855034 | Compared with the old group, VSMCs in the treated groups had a significant increase in p16 protein expression and a significant decrease in cyclinD1, CDK4 and pRb protein expressions (P<0 |
| 22820504 | The expression of p16(INK4A) was significantly increased, whereas levels of CDK4, CDK6 and p-Rb expression were decreased in the MSCs from both untreated and treated SLE patients |
| 22555846 | IS increased the mRNA expression of p53 and p21 in HASMCs, whereas it did not change that of p16 and retinoblastoma protein (pRb) |
| 22496421 | However, activation of either the p53 or pRB tumor suppressor pathway was sufficient to induce lamin B1 loss |
| 22480653 | Notably, several tumour suppressors, such as p53, pRb or p16(Ink4a), play key roles both in the initiation of the senescence program and in its maintenance, which often involves epigenetic changes |
| 22467239 | We first observed that AGR2 was overexpressed in Chinese Han PCa tissues and had a positive correlation with cyclin D1 and p-Rb but not with p16(INK4a) |
| 22392074 | IGFBP-rP1-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21 and dephosphorylation of the retinoblastoma protein (pRB) |
| 22366686 | The molecular underpinnings for this stable arrest involve transcriptional repression of proliferation-promoting genes regulated by the retinoblastoma (RB1)/E2F repressor complex |
| 22366686 | Here, we demonstrate that AGO2, RB1 and microRNAs (miRNAs), as exemplified here by let-7, physically and functionally interact to repress RB1/E2F-target genes in senescence, a process that we call senescence-associated transcriptional gene silencing (SA-TGS) |
| 22358238 | The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction |
| 22358238 | CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts |
| 22358238 | Incubation with gamma-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase |
| 22333593 | The specific role of pRb in p16 (INK4A) -mediated arrest of normal and malignant human breast cells |
| 22333593 | RB family proteins pRb, p107 and p130 have similar structures and overlapping functions, enabling cell cycle arrest and cellular senescence |
| 22333593 | In human fibroblasts acutely exposed to oncogenic ras, pRb has a specific role in suppressing DNA replication, and p107 or p130 cannot compensate for the loss of this function; however, a second p53/p21-dependent checkpoint prevents escape from growth arrest |
| 22333593 | This model of oncogene-induced senescence requires the additional loss of p53/p21 to explain selection for preferential loss of pRb function in human malignancies |
| 22333593 | We asked whether similar rules apply to the role of pRb in growth arrest of human epithelial cells, the source of most cancers |
| 22333593 | In two malignant human breast cancer cell lines, we found that individual RB family proteins were sufficient for the establishment of p16-initiated senescence, and that growth arrest in G 1 was not dependent on the presence of functional pRb or p53 |
| 22333593 | However, senescence induction by endogenous p16 was delayed in primary normal human mammary epithelial cells with reduced pRb but not with reduced p107 or p130 |
| 22333593 | We propose that early inactivation of pRb in pre-malignant breast cells can, by itself, extend proliferative lifespan, allowing acquisition of additional changes necessary for malignant transformation |
| 22155925 | The effects of LB1 silencing on proliferation require the activation of p53, but not pRb |
| 22155925 | However, the induction of premature senescence requires both p53 and pRb |
| 22128747 | The 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 |
| 21980403 | We find that depletion of Jarid1b phenocopies knockdown of Rb1 and that Jarid1b associates with E2f-target genes during cellular senescence |
| 21839870 | Two classical tumor suppressors, p53 and pRB, control cell cycle arrest associated with senescence |
| 21835799 | The repression of both was previously shown to result in activation of their respective tumor suppressor targets, p53 and pRb, and subsequent senescence induction in cervical cancer cells |
| 21740549 | An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence |
| 21720015 | Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by modulating redox status |
| 21720015 | In the present study we aimed to investigate whether ginsenoside Rb1, a major constituent of ginseng, protects endothelial cells from H(2)O(2)-induced endothelial senescence |
| 21720015 | While H(2)O(2) induced premature senescent-like phenotype of human umbilical vein endothelial cells (HUVECs), as judged by increased senescence-associated beta-galactosidase (SA-beta-gal) activity, enlarged, flattened cell morphology and sustained growth arrest, our results demonstrated that Rb1 protected endothelial cells from oxidative stress induced senescence |
| 21720015 | Mechanistically, we found that Rb1 could markedly increase intracellular superoxide dismutase (Cu/Zn SOD/SOD1) activity and decrease the malondialdehyde (MDA) level in H(2)O(2)-treated HUVECs, and suppress the generation of intracellular reactive oxygen species (ROS) |
| 21720015 | Consistent with these findings, Rb1 could effectively restore the protein expression of Cu/Zn SOD, which was down-regulated in H(2)O(2) treated cells |
| 21720015 | Taken together, our data demonstrate that Rb1 exhibits antioxidant effects and antagonizes H(2)O(2)-induced cellular senescence |
| 21518927 | Accordingly, human ALCLs showed no expression of either p16INK4a or pRb |
| 21513159 | The retinoblastoma1 (RB1) gene is the first cloned tumor suppressor gene |
| 21513159 | As a negative regulator of the cell cycle, RB1 gene could maintain a balance between cell growth and development through binding to transcription factors and regulating the expression of genes involved in cell proliferation and differentiation |
| 21513159 | This review summarizes recent advances on the structure, expression, and function of RB1 gene |
| 21465484 | The switch from pRb/p105 to Rb2/p130 in DNA damage and cellular senescence |
| 21465484 | Here, we discuss the functional relevance of the switch from pRb/p105 to Rb2/p130 that becomes apparent when cells enter senescent arrest |
| 21420382 | In addition, HDAC1 overexpression led to senescence through both an accumulation of hypophosphorylated active retinoblastoma protein (pRb) and an increase in the protein level of protein phosphatase 2A catalytic subunit (PP2Ac) |
| 22553621 | Epidemiology and Rb1 gene of retinoblastoma |
| 22553621 | In children with the heritable genetic form of Rb, there is a mutation on chromosome 13, called the retinoblastoma 1 (Rb1) gene |
| 22553621 | The Rb1 gene is the first cloned tumor suppressor gene |
| 22553621 | As a negative regulator of the cell cycle, Rb1 gene could maintain a balance between cell growth and development through binding to transcription factors and regulating the expression of genes involved in cell proliferation and differentiation |
| 22553621 | We summarized the recent advances on the epidemiology and Rb1 gene of Rb in this review |
| 21118958 | DNA-SCARS form independently of p53, pRB and several other checkpoint and repair proteins but require p53 and pRb to trigger the senescence growth arrest |
| 21110788 | Combined knockdown of p21 and pRb resulted in vigorous re-proliferation |
| 21110788 | These results suggest that oxidative stress-induced cellular senescence is registered by multiple p53 target genes, which arrest proliferation redundantly, in part by activating pRb |
| 20819672 | The pathophysiological events such as morphologic alterations, cell senescence, cell proliferation, apoptosis and pRb as well as p53 protein expressions were also investigated in primary fibroblasts |
| 20819672 | Although the senescence-associated beta-galactosidase staining of patient' cells was negative, cells in S phase increased in accompany with a decrease in pRb protein expression |
| 20819672 | The abnormalities in nuclear structure and alterations in gene expression such as the decrease in pRb and increase in p53 may be responsible for the multiple tissue degeneration |
| 20705054 | Senescence growth arrest is known to be controlled by p53 phosphorylation/p21(WAF1/Cip1) induction or p16(INK4a)/retinoblastoma protein (pRB) activation |
| 20705054 | SM22alpha overexpression in HepG2 cells elevated p16(INK4a) followed by pRB activation, but did not activate the p53/p21(WAF1/Cip1) pathway |
| 20554622 | Induction of senescence-related signal transduction proteins (p16, p21, and pRb) was examined by real-time PCR and Western blot analysis |
| 20554622 | TGF-beta2 increased p16 mRNA and protein expression, which was paralleled by a downregulation of pRb protein |
| 20534396 | It has long been known that loss of a key tumour suppressor gene, such as p53 or pRB, is necessary but not sufficient for spontaneous cellular immortalisation |
| 20197380 | These include increased staining of senescence-associated beta-galactosidase, increased nuclear and cell body size, vacuolated cellular morphology, upregulation/stabilization of p53, p21, and hypophosphorylated pRb |
| 20181942 | The retinoblastoma tumor suppressor gene (RB-1) is a key regulator of cellular senescence |
| 20181942 | Expression of the retinoblastoma protein (pRB) in human tumor cells that lack it results in senescence-like changes |
| 20181942 | The induction of the senescent phenotype by pRB requires the postmitotic kinase CDK5, the best known function of which is in neuronal development and postmitotic neuronal activities |
| 20181942 | We demonstrate that: (i) p35 is expressed in osteosarcoma cells, (ii) p35 is required for CDK5 activation induced by pRB during senescence, (iii) p35 is required for the senescent morphological changes in which CDK5 is known to be involved as well as for expression of the senescence secretome, and (iv) p35 is up-regulated in senescing cells |
| 20174572 | We also show that AKT-induced oncogenic senescence is dependent of pRb but not of p53 |
| 20008551 | Here we show that the retinoblastoma protein (pRB) uses a mechanism to block DNA replication in senescence that is distinct from its role in permanent cell cycle exit associated with terminal differentiation |
| 20008551 | Our work demonstrates that a subtle mutation in pRB that cripples its ability to interact with chromatin regulators impairs heterochromatinization and repression of E2F-responsive promoters during senescence |
| 20008551 | Remarkably, this reveals that pRB recruits chromatin regulators primarily to engage a stress-responsive G(1) arrest program |
| 19737973 | Retinoblastoma family members (pRb, p107, and p130) previously implicated in gene silencing during fibroblasts senescence were found down-regulated in cells with nutlin-induced senescence-like phenotype, suggesting a mechanism for its reversibility |
| 19718037 | This response is controlled by tumor suppressor proteins such as p53 and pRb |
| 19540815 | OUTCOME MEASURES: We examined cell senescence markers (senescence-associated beta-galactosidase [SA-beta-gal], telomere length, telomerase activity, p53, p21, pRB, and p16) and the hydrogen peroxide (H(2)O(2)) content as a marker for an oxidative stress in the human NP specimens |
| 19540815 | For the mechanism involved in the senescence of NP chondrocytes, expressions of p53, p21, pRB, and p16 in these cells were assessed with immunohistochemistry and Western blotting |
| 19540815 | Immunohistochemistry showed that the senescent NP chondrocytes in all the specimens expressed p53, p21, and pRB, but a few NP chondrocytes in only two specimens expressed p16 |
| 19540815 | Western blotting showed that the expressions of p53, p21, and pRB displayed a corresponding pattern, that is, a strong p53 expression led to strong p21 and pRB expressions and vice versa |
| 19486941 | In G1, ROS stimulate mitogenic pathways that control the activity of cyclin-dependent kinases (CDKs) and phosphorylation of the retinoblastoma protein (pRB), thereby regulating S-phase entry |
| 19486941 | In S phase, ROS induce S-phase arrest via PP2A-dependent dephosphorylation of pRB |
| 19345325 | Here, we demonstrate that pRb inactivation induces aberrant expression of farnesyl diphosphate synthase, many prenyltransferases, and their upstream regulators sterol regulatory element-binding proteins (SREBPs) in an E2F-dependent manner, leading to enhanced isoprenylation and activation of N-Ras |
| 19345320 | Ras and pRb: the relationship gets yet more intimate |
| 19345320 | Ras and pRb are key regulators of a plethora of cellular processes, including proliferation, differentiation, and tumorigenesis |
| 19171648 | Expression of senescence-associated genes (apolipoprotein J [Apo J], connective tissue growth factor [CTGF], fibronectin, and SM22) was examined by real-time PCR and induction of signal transduction proteins (p21, p16, and pRb) by Western blot analysis |
| 19171648 | H(2)O(2)and TGF-beta1 and -beta2 markedly enhanced the expression of p21 but downregulated pRb |
| 19169823 | Cellular senescence is a potent anti-cancer mechanism controlled by tumor suppressor genes, particularly p53 and pRb, which is characterized by the irreversible loss of proliferation |
| 19070423 | Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation |
| 18948382 | Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS |
| 18948382 | Suppressing both the p53 and pRb pathways resulted in almost complete protection, indicating that both pathways cooperate in hyperoxia-induced senescence |
| 18836456 | Knockdown of Jhdm1b in primary mouse embryonic fibroblasts inhibits cell proliferation and induces cellular senescence in a pRb- and p53 pathway-dependent manner |
| 18800172 | PPP1CA is induced by Ras; its inactivation inhibits Ras-induced senescence, presumably by inhibiting pRb dephosphorylation |
| 18800172 | Finally, PPP1CA seems to strongly co-localize with pRb only during senescence |
| 18800172 | PPP1CA is induced by Ras; its inactivation inhibits Ras-induced senescence, presumably by inhibiting pRb dephosphorylation |
| 18800172 | Finally, PPP1CA seems to strongly co-localize with pRb only during senescence, suggesting that PP1alpha activation during senescence may be the second signal contributing to the irreversibility of the senescent phenotype |
| 18701096 | Western blot confirmed down-regulation of phosphorylated retinoblastoma protein (pRB) and up-regulation of p53 in IGFBP-rP1-transfectants as compared with control cells |
| 18701096 | Our results uncovered a novel molecular mechanism involving the altered expression of pRB and p53 for tumor suppressor gene IGFBP-rP1 in colorectal cancer |
| 18628455 | RESULTS: TAC populations showed increased expression of p53, p21, p16, and pRb, resulting in senescence |
| 20411135 | METHODS: We examined cell senescence markers [senescence-associated beta-galactosidase (SA-beta-gal), telomere length, telomerase activity, p53, p21, pRB and p16] and the hydrogen peroxide (H(2)O(2)) content in human NP specimens |
| 20411135 | Immunohistochemistry showed that senescent NP chondrocytes in all specimens expressed p53, p21, and pRB, while a few NP chondrocytes in only two specimens expressed p16 |
| 20411135 | Furthermore, the telomere-based p53, p21, pRB pathway, rather than the stress-based p16, pRB pathway, plays a more important role in the senescence of NP chondrocytes in in vivo conditions |
| 18271016 | Consistent with activation of the pRb proteins, E2F-responsive genes such as cyclin A are repressed in EWS/FLI1-depleted cells |
| 17643369 | Repression of Wnt2 occurs early in senescence and independently of the pRB and p53 tumor suppressor proteins and drives relocalization of HIRA to PML bodies, formation of SAHF and senescence, likely through GSK3beta-mediated phosphorylation of HIRA |
| 17586029 | Furthermore, the downregulation of HPV-16 E6 and E7 by 16AS transfection resulted in remarkable increase of both p53 expression and hypophosphorylated p105Rb level in SiHa cells |
| 17428679 | Here, we have used indirect immunofluorescence and confocal microscopy to describe various forms of a novel nuclear PML compartment associated with nucleoli that is found under growth-permitting conditions in human mesenchymal stem cells (hMSC) and skin fibroblasts but not in several immortal cell lines with defects in the p53 and pRb pathways |
| 17343761 | The retinoblastoma (Rb) tumor suppressor gene product, pRb, has an established role in the implementation of cellular senescence, the state of irreversible G1 cell cycle arrest provoked by diverse oncogenic stresses |
| 17343761 | In murine cells, senescence cell cycle arrest can be reversed by subsequent inactivation of pRb, indicating that pRb is required not only for the onset of cellular senescence, but also for the maintenance of senescence program in murine cells |
| 17343761 | However, in human cells, once pRb is fully activated by p16INK4a, senescence cell cycle arrest becomes irreversible and is no longer revoked by subsequent inactivation of pRb, suggesting that p16INK4a/Rb-pathway activates an alternative mechanism to irreversibly block the cell cycle in human senescent cells |
| 17274801 | This finding is supported by distributions of modified pRb in the laminopathy cells |
| 17242198 | Cellular senescence is an irreversible proliferation arrest triggered by short chromosome telomeres, activated oncogenes, and cell stress and mediated by the pRB and p53 tumor suppressor pathways |
| 17242198 | Significantly, translocation of HIRA to PML bodies occurs in the absence of functional pRB and p53 tumor suppressor pathways |
| 17242198 | However, our evidence indicates that downstream of HIRA's localization to PML bodies, the HIRA/ASF1a pathway cooperates with pRB and p53 to make SAHF, with the HIRA/ASF1a and pRB pathways acting in parallel |
| 17242198 | We present evidence that convergence of the HIRA/ASF1a and pRB pathways occurs through a DNAJ-domain protein, DNAJA2 |
| 17016587 | The characteristics of proliferation and metastasis were shown by PCNA (proliferating cell nuclear antigen), and nm23 and cell cycle-related genes, such as p16, p21, p53 and pRb, were analyzed by RT-PCR and immunohistochemistry |
| 17016587 | The cell cycle-related genes, such as p16, p21, p53 and pRb, were not detected in F6 cells, while the expression of hTRAP and BMI-1 was significantly higher |
| 16936745 | Here, we summarize the pathways, which specify pRb2/p130 to control this arrest program and distinguish its functions from those of pRb/p105 |
| 16803991 | A small subset of the senescent cells showed aberrant morphology such as remarkable nuclear fragmentation or multiple micronuclei, and such cells often showed positive reactions with antibody to phosphorylated pRb |
| 16794190 | VSMC senescence was mediated by changes in cyclins D/E, p16, p21, and pRB, and plaque VSMCs could reenter the cell cycle by hyperphosphorylating pRB |
| 16609829 | Venous ulcer fibroblasts show phenotypic similarity to senescent cells, with overexpression of p21 as well as down regulation of phosphorylated pRb |
| 16510591 | Consistent with an antioncogenic role in this process, the tumor suppressor pRb plays a critical role in senescence |
| 16510591 | Reexpression of pRb in human tumor cells results in senescence-like changes, including cell cycle exit and cell shape alteration |
| 16456675 | In addition, as pan-cell cycle regulator TIS21 induces G1/S arrest by pRB dependently and pRB independently and G2/M arrest and cell death in the p53 null tumor cells, and regulates the development of vertebrate patterning in mouse, paraxial mesoderm development in zebrafish, and notochord development in Xenopus |
| 16456675 | The latter has already been well elucidated; TIS21 inhibits the expression of cyclin D1, thus resulting in the arrest of cells at G1/S phase by pRB and p53 dependent manner |
| 16123778 | To determine pathways cooperating with p53 in cellular senescence when the retinoblastoma protein (pRb)/p16INK4a pathway is defunct, we stably transfected the p16INK4a-negative C6 rat glioma cell line with a temperature-sensitive mutant p53 |
| 16123778 | Activation of p53(Val-135) induces a switch in pocket protein expression from pRb and p107 to p130(Rb2) and stalls the cells in late G1, early S-phase at high levels of cyclin E |
| 16123778 | The data indicate that p53 can cooperate selectively with p130(Rb2) to induce cellular senescence, a pathway that may be relevant when the pRb/p16INK4a pathway is defunct |
| 15885198 | Loss of p53 and pRb function allows continued cell division despite increasing telomere dysfunction and eventually entry into telomere crisis |
| 15716376 | Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53 |
| 15530855 | In human fibroblasts, suppressing both the p53 and pRb pathways is necessary to bypass replicative senescence as well as senescence induced by ectopic expression of a dominant negative form of the telomere repeat binding factor 2, TRF2(DN) |
| 15530855 | We recently reported that exposure to oligonucleotides homologous to the telomere 3' overhang (T-oligos) activates both the p53 and pRb pathways and leads to senescence in primary human fibroblasts |
| 15530855 | To further characterize T-oligo-induced senescence, we compared established isogenic fibroblast cell lines lacking functional p53 and/or pRb pathways to the normal parental line |
| 15530855 | Here, we report that, as in physiologic senescence, inactivation of both the p53 and pRb pathways is necessary to suppress T-oligo-induced senescence |
| 15467458 | On the other hand, in a tumor cell in which neither the p53 nor pRb pathway is intact, shortened telomeres could initiate chromosome instability and promote tumorigenesis A major issue in telomere research is to understand how shortened dysfunctional telomeres can regulate the onset of cellular senescence |
| 15389598 | Down-regulation of p21(WAF1) by antisense caused an increase in the phosphorylation and inactivation of pRb |
| 15389598 | Phosphorylation of pRb was further enhanced upon induction of apoptosis by NaBu |
| 15389598 | Our results suggest that p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli |
| 15138605 | Stable expression of p16INK4a suppressed the malignant phenotype in MCF-7 cells, including cell proliferation, anchorage-independent growth, G1/G0 cell cycle arrest, and the blockage of pRB phosphorylation |
| 15138376 | In this Review article, we categorize cellular senescence into two types, which for simplicity we term intrinsic or extrinsic senescence, focus on the differences between human and mouse cells, and discuss the roles of the p53 and pRb tumor suppressor pathways in cellular senescence |
| 15024070 | CDK5 regulation of Rac1 activity is necessary for actin polymerization accompanying senescent morphology in response to expression of pRb, activated Ras, or continuous passage |
| 14729964 | It was suggested that the direct interaction of BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle progression by pRB |
| 14729964 | Furthermore, we show that the physical interaction between BRG1 and pRB is not required for induction of cell growth arrest and transcriptional repression of E2F target genes by pRB |
| 14729964 | Instead, BRG1 activates pRB by inducing its hypophosphorylation through up-regulation of the cdk inhibitor p21 |
| 14729964 | The hypophosphorylation of pRB is reinforced by down-regulation of critical components, including cdk2, cyclin E, and cyclin D, in the pRB regulatory network |
| 14729964 | Our results suggest that the BRG1-containing complexes control cellular proliferation and senescence by modulating the pRB pathway via multiple mechanisms |
| 14504464 | Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the retinoblastoma tumor suppressor protein, pRb |
| 14504464 | We have recently discovered that expression of active pRb induces expression and altered localization of the ERM family member ezrin, an actin-binding protein involved in membrane-cytoskeletal signaling |
| 12939397 | Senescent cells in which pRb is inactivated undergo apoptosis on attempted reinitiation of DNA synthesis |
| 12939397 | To further explore the cell death resulting from loss of pRb function in senescent cells, we employed a temperature-sensitive pRb mutant protein (tspRb) |
| 12939397 | Total inhibition of cyclin-dependent kinase 2 activity results in a cell cycle arrest on pRb loss and a nearly complete suppression of apoptosis |
| 12939397 | Finally, inhibition of p73 activity abolishes apoptosis but not S-phase entry on pRb inactivation, suggesting that activation of E2F in senescent cells can result in the use of p73 as a cell death effector |
| 12912919 | Replicative senescence is thought to suppress tumorigenesis by establishing an essentially irreversible growth arrest that requires activities of the p53 and pRB tumor suppressor proteins |
| 12912919 | We show that, depending on expression of the pRB regulator p16, replicative senescence is not necessarily irreversible |
| 12912919 | In contrast, cells with high levels of p16 at senescence failed to proliferate upon p53 inactivation or RAS expression, although they re-entered the cell cycle without growth after pRB inactivation |
| 12836417 | In fibroblasts, senescence is induced by telomere attrition and depends on p53 and pRb pathways triggered by one or a few critically short telomeres |
| 12836417 | Possible explanations for these discordant results are that better growth conditions avoided culture-induced stress in the study with clones, or that clones had undergone alterations leading, for example, to the inactivation of the pRb pathway during their derivation |
| 12769842 | Consistent with an anti-oncogenic role for this process, the tumor suppressor pRb plays a critical role in senescence |
| 12769842 | Reexpression of pRb in human tumor cells results in senescence-like changes including cell cycle exit and shape changes |
| 12756294 | The expression of E2 in HPV-positive cancer cells results in the repression of the viral E6/E7 oncogenes, activation of the p53 and pRB pathways, and a G1 cell cycle arrest, followed by induction of cellular senescence |
| 12750549 | The retinoblastoma protein pRb is functionally inactivated in most human cancers |
| 12750549 | Numerous studies in cell culture and animal models suggest that pRb has a unique ability to encourage and enforce permanent cell cycle withdrawal, consistent with its role as a tumor suppressor protein |
| 12750549 | In addition, numerous studies hint at additional specific roles for pRb in differentiation of certain tissue types |
| 12750549 | Further, pRb appears to play a central role in the process of cellular senescence, a tumorsuppressive process characterized by proliferative arrest and phenotypic changes |
| 12750549 | Both differentiation and senescence pathways influenced by pRb involve direct and indirect interactions with the core machinery involved in cell-type-specific differentiation and cell shape control |
| 12750549 | In addition, novel pathways activated by pRb in its role as an inducer of cellular senescence will be discussed |
| 12615976 | This was associated with hypophosphorylated pRb and high levels of p16(Ink4a) and p21(Waf1) |
| 12414954 | At the molecular level, cells infected by HCMV, beside the accumulation of large amounts of the cell cycle regulators p53 and pRb, the latter in its hyperphosphorylated form, display a strong induction of the cyclin-dependent kinase inhibitor (cdki) p16(INK4a), a direct effector of the senescence phenotype in fibroblasts, and a decrease of the cdki p21(CIP1/WAF) |
| 12414655 | The tumor suppressor genes p16(INK4A), pRb, and p53 have been implicated in the induction of cellular senescence |
| 11840324 | Two such proteins, pRB (retinoblastoma tumour suppressor protein) family proteins and Ets-family transcription factors are known to play key roles in cell cycle regulation, transformation and tumour suppression |
| 11791184 | A pRb immunoprecipitation demonstrated more binding of E2F-1 to pRb in the high expressing IGFBP-rP1/mac25 clones than in control cells |
| 11756559 | Cdk4(R24C/R24C) mouse embryo fibroblasts (MEFs) displayed increased Cdk4 kinase activity resulting in hyperphosphorylation of all three members of the Rb family, pRb, p107, and p130 |
| 11714633 | Repression of the human papillomavirus (HPV) type 18 E6/E7 genes in HeLa cells by the bovine papillomavirus E2 transcriptional regulatory protein results in reactivation of the dormant p53 and p105(Rb) tumor suppressor pathways in these cells, repression of telomerase, and profound growth arrest |
| 11668507 | NaB-mediated p21 might arrest endometrial and ovarian cancer cells at the G0/G1 phase by eliciting pRb unphosphorylation |
| 11668507 | To demonstrate the role of pRb regulation by p21, we measured the sensitivity to NaB of cervical cancer cells in which pRb had been inactivated by HPV E7 |
| 11668507 | Most importantly, the effect of NaB on senescence induction was not coupled with the predominance of hypophosphorylated pRb forms in the cervical cancer cells |
| 11407594 | The unique INK4A/ARF locus at chromosome 9p21 encodes two distinct proteins that intimately link the pRB and p53 tumour suppressor pathways |
| 11349961 | Normal somatic cells terminate their replicative life span through a pathway leading to cellular senescence, which is triggered by activation of p53 and/or pRb in response to critically shortened telomere DNA |
| 11060027 | Papillomavirus E2 induces senescence in HPV-positive cells via pRB p21(CIP)-dependent pathways |
| 10962000 | Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence |
| 10958672 | At the end of lifespan, terminal-passage E6 cells exhibited several aspects of the senescent phenotype and accumulated unphosphorylated pRb and p16 |
| 10958672 | Similarly, when p21(-/-) mouse embryo fibroblasts reached the end of their lifespan, they had the appearance of senescent cells yet, in contrast to their wild-type counterparts, they were deficient in downregulating bromodeoxyuridine incorporation, cyclin E- and cyclin A-Cdk2 activity, and inhibiting pRb hyperphosphorylation |
| 10911949 | Here we demonstrate that in melanocytes derived from dark-skinned individuals, CT-induced melanogenesis is associated with accumulation of the tumor suppressor p16INK4a, underphosphorylated retinoblastoma protein (pRb), downregulation of cyclin E, decreased expression of E2F1, and loss of E2F-regulated S-phase gene expression |
| 10911949 | This delayed senescence may result from reduced association of p16 with CDK4, reduced levels of underphosphorylated pRb, and steady levels of cyclin E and E2F1 |
| 10648922 | One induces irreversible cell cycle exit involving activation of two tumorsuppressor genes, p53 and pRb, and the proper time point is indicated by a critical shortening of chromosomal ends due to the end-replication problem of DNA synthesis |
| 10585280 | Here we present evidence that activation of a cAMP pathway correlates with multiple cellular changes in these cells: (1) increased expression of the transcription factor microphthalmia; (2) increased melanogenesis; (3) increased association of the cyclin-dependent kinase inhibitors (CDK-Is) p27(KIP1) and p16(INK4) with CDK2 and CDK4, respectively; (4) failure to phosphorylate the retinoblastoma protein (pRB); (5) decreased expression of E2F1, E2F2, and E2F4 proteins; (6) loss of E2F DNA-binding activity; and (7) phenotypic changes characteristic of senescent cells |
| 10537318 | One of these groups is associated with the predominance of underphosphorylated, growth-suppressive retinoblastoma tumor suppressor protein (pRb) |
| 10537318 | Although certain members of the cyclin-dependent kinase (cdk)/cyclin family, some of which phosphorylate pRb, are underexpressed in senescent cells, others are expressed but inactive |
| 10094825 | These effects on myoblast differentiation could be related in part to the level of retinoblastoma protein (pRb), the major cellular target of E7 |
| 10094825 | These results support a key role for pRb in the acquisition and maintenance of the differentiated state in human skeletal muscle and, in cooperation with p53, in the control of proliferative capacity and response to external growth factors |
| 10022898 | The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb) |
| 10022898 | Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16 |
| 9916803 | In addition, co-expression of telomerase, the viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS does not result in growth in soft agar |
| 9732051 | Serum stimulated senescent HDF fail to phosphorylate their retinoblastoma protein (pRb) and consequently do not express a large cohort of late G1 phase genes whose products are necessary for entry into S phase |
| 9732051 | Because pRb is believed to be phosphorylated sequentially in G1 phase by cyclin D-CDK4/6 and cyclin E-CDK2 complexes, we and others have investigated the status of these complexes in senescent HDF |
| 9546379 | The tumor suppressor genes p105RB (retinoblastoma, acting through the E2F transcription factor family) and p53 regulate cell proliferation, cell senescence, and apoptosis in many cell types |
| 9512419 | These include a reduced proliferative capacity, an altered size and shape, the presence of underphosphorylated retinoblastoma protein (pRb), increased expression of plasminogen activator inhibitor (PAI-1) and the appearance of senescence-associated beta-galactosidase (SA-beta-gal) activity [2,3,13-15] |
| 9436977 | Immortal HUCs and bladder cancer cell lines show either alteration of p16 or pRb, the product of the retinoblastoma (RB) TSG |
| 9436977 | In addition, many human cancers show p16 or pRb alteration along with other genetic alterations that we associated with immortalization, including +20q and -3p |
| 9436977 | Using a novel approach, we tested these hypotheses in the present study by examining p16 and pRb status in primary culture (P0) and after passage in vitro of transitional cell carcinoma (TCC) biopsies that represented both superficial bladder tumors and invasive bladder cancers |
| 9436977 | In contrast, all muscle invasive TCCs contained either a p16 or a pRb alteration at P0 and all spontaneously bypassed senescence (P = 0 |
| 9436977 | Thus, these data support a new model in which overcoming senescence plays a critical role in human cancer pathogenesis and requires at least two genetic changes that occur in several combinations that can include either p16 or pRb loss and at least one additional alteration, such as +20q11-q12, -3p13-p14, or -8p21-pter |
| 9399646 | We demonstrate here that reexpression of functional pRB alone in RB/p53-defective tumor cells via a modified tetracycline-regulated gene expression system resulted in a stable growth arrest at the G0/G1 phase of the cell cycle, preventing tumor cells from entering S phase in response to a variety of mitogenic stimuli |
| 9399646 | Further studies indicated that telomerase activity, which was assumably essential for an extended proliferative life-span of neoplastic cells, was abrogated or repressed in the tumor cell lines after induction of pRB (but not p53) expression |
| 9399646 | Strikingly, when returned to an non-permissive medium for pRB expression, the pRB-induced senescent tumor cells resumed DNA synthesis, attempted to divide but most died in the process, a phenomenon similar to postsenescent crisis of SV40 T-antigen-transformed human diploid fibroblasts in late passage |
| 9399646 | These observations provide direct evidence that overexpression of pRB alone in RB/p53-defective tumor cells is sufficient to reverse their immortality and cause a phenotype that is, by all generally accepted criteria, indistinguishable from replicative senescence |
| 9399646 | The results suggest that pRB may play a causal role in the intrinsic cellular senescence program |
| 8893868 | Alterations in p53 and pRb, products of the chromosomes 17p13 TP53 and 13q14 RB tumor suppressor genes, occur in approximately 50% and approximately 33% of bladder cancers respectively, and are associated with later stage, higher grade disease |
| 8817002 | We examined c-fos expression during the entire lifespan of normal human fibroblasts carrying E6 (which binds p53), E7 (which binds pRB), or both E6 and E7 of human papilloma virus type 16 |
| 8622687 | Human cell lines lacking functional pRB contain high levels of p16 RNA and protein, suggesting a negative feedback loop by which pRB might regulate p16 expression in late G1 |
| 8622687 | By a combination of nuclear run-on assays and promoter analyses in human fibroblasts expressing a temperature-sensitive simian virus 40 T antigen, we show that p16 transcription is affected by the status of pRB and define a region in the p16 promoter that is required for this response |
| 8622687 | The apparent overexpression of p16 in pRB-negative cell lines is therefore caused by at least two factors: loss of repression by pRB and an increase in the number of population doublings |
| 21544354 | The human papillomavirus (HPV) oncoproteins, HPV-16 E6 and E7, can block the progression to senescence in fibroblasts by associations with p53 and pRb, respectively |
| 21544354 | Human mammary epithelial (HME) cells require only HPV-16 E6 to bypass M1, suggesting that pRb may not have a direct role in HME cells senescence |
| 9114431 | This review outlines the intrinsic inhibitory signal pathways that link this clock to cell cycle arrest, focussing on the role of tumour suppressor gene products, particularly the p53 and pRb proteins |
| 8934878 | The only genes known to reactivate DNA synthesis in senescent cells are viral oncogenes encoding proteins that bind and inactivate the p53 and retinoblastoma (pRb) tumor suppressor proteins |
| 8934878 | T[K1] is a T antigen point mutant that selectively is defective in binding pRb and the pRb-related proteins p107 and p130 |
| 8934878 | It did not appear that Id-1 interacted directly with pRb or p107 |
| 8934878 | Constitutive Id-1 expression failed to rescue proliferating cells from growth inhibition by pRb, p107, or p130, and failed to interact with pRb in the yeast two hybrid system |
| 8934878 | Because Id proteins negatively regulate basic-HLH (bHLH) transcription factors, we suggest that senescent cells express one or more bHLH factor that cooperates with pRb, or pRb-related proteins, to suppress proliferation |
| 8706800 | These effects are mediated through inactivation of function of growth suppressors pRB and p53 via complex formation with T antigen |
| 7698220 | Substrates for cyclin D1/Cdks have not been identified in vivo, but it has been proposed that the D class of cyclins might play a role in regulating the activity of the retinoblastoma gene product p105Rb |
| 7542356 | Such a specific lack of cdk2 and cyclin E proteins correlated with unphosphorylation of the retinoblastoma gene product (pRB) in senescent cells |
| 7542356 | Middle-passage cells exhibited active expressions of all the above genes and pRB phosphorylation |
| 7937901 | The retinoblastoma (RB) gene encodes a nuclear phosphoprotein of 928 amino acids (pRB) |
| 7937901 | We report here that an N-terminal truncated RB protein of approximately 94 kDa (pRB94) exerts more potent cell growth suppression as compared to the full-length pRB protein in a diversity of tumor cell lines examined, including those having a normal endogenous RB gene |
| 7937901 | The pRB94 expressed in recipient tumor cells had a longer half-life than the full-length pRB protein and tended to remain in an active un- or hypophosphorylated form |
| 7937901 | Since it has also been found that N-terminal truncated RB proteins often accumulated in growth-arrested and/or differentiated tumor cells, we suggest that N-terminal truncation of pRB may be one of the cellular mechanisms modulating the RB protein function in cell-cycle control |
| 7958891 | HPV16 E6 binds p53, leading to rapid degradation of p53, whereas E7 binds and alters pRb and other proteins |
| 7958891 | These results implicate p53 loss, but not pRb alteration, in genome destabilization |
| 8174635 | This TFIID complex was present in quiescent cells, but absent from four human cell lines that lack a functional retinoblastoma protein (pRb); both pRb-specific and TFIID-specific antibodies selectively disrupted it |
| 8174635 | The data suggest that an altered profile of transcription factors may specify the senescent phenotype and that pRb may interact with TFIID or a TFIID-associated protein(s) |
| 1297331 | We find that cyclin A and p34cdc2 expression is decreased by two- to four-fold in old fibroblasts, but that Fos expression and binding activity are reduced by as much as 95% in old, as opposed to young cells, despite equivalent amounts of p105Rb and Jun proteins being expressed |
| 1826560 | We have examined the functional consequences of mutations present in defective alleles of the retinoblastoma susceptibility gene (RB1) isolated from two spontaneously arising tumors |
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