RB1 Protein, Human (StrepⅡ)

Rb (Retinoblastoma protein) is a critical tumor suppressor that regulates the G1/S transition of the cell cycle. The hypophosphorylated form binds E2F family transcription regulators, repressing E2F-responsive gene transcription. Rb not only physically blocks E2F's transactivation domain but also recruits chromatin-modifying enzymes (e.g., histone methyltransferases SUV39H1, KMT5B, and KMT5C) to actively repress transcription, maintaining heterochromatin structure, particularly constitutive heterochromatin, and controlling histone H4 'Lys-20' trimethylation. CDK/cyclin-dependent phosphorylation induces Rb dissociation from E2F, activating E2F-responsive genes and triggering S-phase entry. Additionally, Rb promotes the G0-G1 transition upon phosphorylation by CDK3/cyclin-C. In neurons, Rb collaborates with SMARCA4/BRG1 to recruit an HDAC complex, repressing c-FOS promoter transcription; calcium influx triggers calcineurin-mediated Rb dephosphorylation, releasing the repressor complex (By similarity). During viral infection, SV40 large T antigen, HPV E7, or adenovirus E1A disrupts the Rb-E2F1 complex, impairing Rb's function.