RB1
GeneName
RB1
Summary
RB1, also known as pRb, RB-1, or p104, is a 106 kDa tumour suppressor protein that plays a critical role in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. It is predominantly localised in the nucleus and is involved in chromatin remodelling and transcriptional regulation. RB1 binds to various proteins, including DNA-binding transcription factors and kinases, to exert its function as a transcriptional corepressor. The protein is integral to processes such as cell differentiation, apoptosis, and maintenance of genomic stability, and it is expressed in a variety of tissues, including those undergoing rapid cell division. Its interactions within the Rb-E2F complex are essential for controlling gene expression related to cell cycle progression and differentiation.
Importance
RB1 is relevant to: - Cancer research, particularly in understanding retinoblastoma and other malignancies, due to its role in cell cycle regulation and tumour suppression - Developmental biology, as it influences processes like neuron differentiation and muscle cell development - Studies on cellular responses to various stimuli, including insulin and xenobiotics, contributing to insights into metabolic disorders - Epigenetics and chromatin dynamics, given its involvement in chromatin remodelling and transcriptional regulation
Top Products
For researchers investigating RB1, we highly recommend the top-selling recombinant antibody, Anti-Rb antibody [EPR17512] (ab181616). This well-cited product has garnered 101 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). This versatility makes it an excellent choice for those seeking reliable and consistent detection of RB1 in their experiments.
Abcam Product Citation Summary
The data indicates that the RB1 target is being investigated in the context of cellular senescence, specifically using human WI-38 cells. This suggests a focus on the role of RB1 in regulating cell cycle and senescence mechanisms.
Abcam Product Citation Table
Domain
The Pocket domain binds to the threonine-phosphorylated domain C, thereby preventing interaction with heterodimeric E2F/DP transcription factor complexes.
Function
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.
Involvement in disease
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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Osteogenic sarcoma
OSRC
A sarcoma originating in bone-forming cells, affecting the ends of long bones.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
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.
Sequence Similarities
Belongs to the retinoblastoma protein (RB) family.
Tissue Specificity
Expressed in the retina. Expressed in foreskin keratinocytes (at protein level) (PubMed:20940255).
Cellular localization
- Nucleus
- Cytoplasm
- During keratinocyte differentiation, acetylation by KAT2B/PCAF is required for nuclear localization (PubMed:20940255). Localizes to the cytoplasm when hyperphosphorylated (By similarity).
Alternative names
Retinoblastoma-associated protein, p105-Rb, p110-RB1, pRb, pp110, Rb, RB1
Database links
Other research areas
- Immuno-oncology