Prb

pRB, or the retinoblastoma protein, is a tumor suppressor encoded by the RB1 gene on chromosome 13q14. It regulates the G1 to S phase transition by binding E2F transcription factors in its hypophosphorylated state, forming a repressor complex that blocks transcription of S-phase genes. pRB also participates in chromatin remodeling and differentiation, and it can influence the DNA damage response. The protein can be inactivated by viral oncoproteins such as HPV E7, which binds the pocket domain and disrupts its function.

Cell cycle–dependent phosphorylation controls pRB activity. Cyclin D–CDK4/6 and cyclin E–CDK2 sequentially phosphorylate pRB during G1; hyperphosphorylation releases E2F and permits S-phase entry. Dephosphorylation by phosphatases can restore pRB function and enforce G1 arrest. pRB activity is modulated by CDK inhibitors like p16INK4a, which block pRB phosphorylation, maintaining growth suppression. Additional modifications, including ubiquitination and acetylation, tune its activity and interactions with chromatin factors.

RB1 mutations cause retinoblastoma, typically following Knudson’s two-hit model; germline mutations predispose to bilateral disease, with somatic loss of the remaining RB1 allele in tumor cells. Beyond retinoblastoma, RB1 loss contributes to various cancers and disrupts cell cycle control, differentiation, and genomic stability. The RB family also includes p107 and p130, pocket proteins that share E2F binding and help regulate the G1/S transition.