Anti-Rb (Ab-807)

Rb operates in the midst of the cell cycle clock apparatus. Its main role is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery (Ref.1). It plays an important role in the Rb/ E2F pathway in cell proliferation, cell fate determination, and cancer (Ref.2). Cellular senescence is a stable form of cell cycle arrest that limits proliferation of damaged cells and act as a natural barrier to cancer progression. A distinct heterochromatic structure that accumulates in senescent human fibroblasts, designated as SAHF (Senescence-Associated Heterochromatic Foci). SAHF formation coincides with recruitment of heterochromatin proteins and the Rb protein to E2F-responsive promoters and is associated with the stable repression of E2F target genes. Both SAHF formation and the silencing of E2F target genes depended on the integrity of the Rb pathway and do not occur in reversibly arrested cells (Ref.3). Rb activates transcription of the c-Jun gene through the SP1-binding site within the c-Jun promoter Protein 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. [The UniProt Consortium]