Retinoblastoma protein 1 (RB1)

Retinoblastoma protein 1 (RB1) is a critical tumor suppressor that acts as a gatekeeper for the G1/S phase transition of the cell cycle (UniProt P06400). It functions primarily by binding and inhibiting E2F transcription factors, which are necessary for the expression of genes involved in DNA replication (PubMed: 29033130). The activity of RB1 is regulated by its phosphorylation state; hypophosphorylated RB1 is active and growth-suppressive, while phosphorylation by CDK4/6 kinases inactivates the protein and allows cell cycle progression (PubMed: 30858515). An RB1 pathway defect refers to the functional loss of this protein, often through genetic mutations or deletions, which leads to unchecked cellular proliferation and is a hallmark of cancers such as small cell lung cancer and triple-negative breast cancer (PubMed: 31160637). While functional RB1 is required for the efficacy of CDK4/6 inhibitors like palbociclib, RB1-deficient tumors are increasingly targeted via synthetic lethal approaches using Aurora kinase or PARP inhibitors (Cancer Discovery 2019). Consequently, evaluating RB1 status is vital for predicting drug response and selecting appropriate therapeutic interventions in oncology.

Other names

pRbRBp105-RbRetinoblastoma-associated proteinPP105

CDK4/6 inhibitors prevent RB1 phosphorylation to maintain cell cycle arrest; in RB1-deficient contexts, synthetic lethal inhibitors (e.g., Aurora kinase or PLK1 inhibitors) are used to induce mitotic catastrophe.