RB1

The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

RB Transcriptional Corepressor 1

Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802).
The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802).
Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802).
Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802).
RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261).
Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity).
(Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity.

Aortic valve morphogenesisISS:BHF-UCL
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell divisionIEA:Ensembl
Cell morphogenesis involved in neuron differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to insulin stimulusIEA:Ensembl
Cellular response to xenobiotic stimulusIEA:Ensembl
Chondrocyte differentiationIEA:Ensembl
Chromatin remodelingManual Assertion Based On ExperimentTAS:BHF-UCL
Digestive tract developmentIEA:Ensembl
Enucleate erythrocyte differentiationIEA:Ensembl
Glial cell apoptotic processIEA:Ensembl
Hepatocyte apoptotic processIEA:Ensembl
Heterochromatin assemblyManual Assertion Based On ExperimentIDA:ComplexPortal
Maintenance of mitotic sister chromatid cohesionManual Assertion Based On ExperimentIMP:BHF-UCL
Myoblast differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of apoptotic signaling pathwayBy SimilarityISS:ARUK-UCL
Negative regulation of cell cycleBy SimilarityISS:ARUK-UCL
Negative regulation of cell growthISS:UniProtKB
Negative regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Negative regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:ComplexPortal
Negative regulation of epithelial cell proliferationIEA:Ensembl
Negative regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of gene expressionManual Assertion Based On ExperimentIMP:MGI
Negative regulation of hepatocyte apoptotic processIEA:Ensembl
Negative regulation of inflammatory responseISS:BHF-UCL
Negative regulation of myofibroblast differentiationISS:BHF-UCL
Negative regulation of protein kinase activityManual Assertion Based On ExperimentIPI:UniProtKB
Negative regulation of protein serine/threonine kinase activityBy SimilarityISS:ARUK-UCL
Negative regulation of smoothened signaling pathwayIEA:Ensembl
Negative regulation of tau-protein kinase activityBy SimilarityISS:ARUK-UCL
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentTAS:BHF-UCL
Negative regulation of transcription involved in G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentTAS:BHF-UCL
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Neuron apoptotic processIEA:Ensembl
Neuron maturationIEA:Ensembl
Neuron projection developmentManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of collagen fibril organizationISS:BHF-UCL
Positive regulation of extracellular matrix organizationISS:BHF-UCL
Positive regulation of macrophage differentiationIEA:Ensembl
Positive regulation of mitotic metaphase/anaphase transitionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of transcription by RNA polymerase IIIEA:Ensembl
Positive regulation of transcription regulatory region DNA bindingManual Assertion Based On ExperimentIDA:MGI
Protein localization to chromosome, centromeric regionManual Assertion Based On ExperimentIMP:BHF-UCL
Ras protein signal transductionManual Assertion Based On ExperimentIEP:BHF-UCL
Regulation of cell cycleManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of centromere complex assemblyManual Assertion Based On ExperimentTAS:BHF-UCL
Regulation of cohesin loadingManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of lipid kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mitotic cell cycleManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of transcription, DNA-templated1 PublicationNAS:UniProtKB
Sister chromatid biorientationManual Assertion Based On ExperimentIMP:BHF-UCL
Skeletal muscle cell differentiationIEA:Ensembl
SpermatogenesisIEA:Ensembl
Striated muscle cell differentiationIEA:Ensembl
Tissue homeostasisIEA:Ensembl

Nucleus
During keratinocyte differentiation, acetylation by KAT2B/PCAF is required for nuclear localization.

Childhood cancer retinoblastoma (RB):
Congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.
Bladder cancer (BLC):
A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences.
Osteogenic sarcoma (OSRC):
A sarcoma originating in bone-forming cells, affecting the ends of long bones.

Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-567 in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. SV40 large T antigen, HPV E7 and adenovirus E1A bind to the underphosphorylated, active form of pRb. Phosphorylation at Thr-821 and Thr-826 promotes interaction between the C-terminal domain C and the Pocket domain, and thereby inhibits interactions with heterodimeric E2F/DP transcription factor complexes. Dephosphorylated at Ser-795 by calcineruin upon calcium stimulation. CDK3/cyclin-C-mediated phosphorylation at Ser-807 and Ser-811 is required for G0-G1 transition. Phosphorylated by CDK1 and CDK2 upon TGFB1-mediated apoptosis.
N-terminus is methylated by METTL11A/NTM1 (By similarity).
Monomethylation at Lys-810 by SMYD2 enhances phosphorylation at Ser-807 and Ser-811, and promotes cell cycle progression. Monomethylation at Lys-860 by SMYD2 promotes interaction with L3MBTL1.
Acetylated during keratinocyte differentiation. Acetylation at Lys-873 and Lys-874 regulates subcellular localization. Can be deacetylated by SIRT1.