RB1

The RB1 gene encodes the retinoblastoma protein (pRB), a pivotal tumor suppressor also known as p105-Rb. It controls cell cycle progression by sequestering E2F transcription factors, inhibiting G1-to-S phase transition. Its activity is regulated via phosphorylation: unphosphorylated pRB binds E2F to repress target genes, while CDK4/6-cyclin D complexes phosphorylate pRB, releasing E2F to drive cell cycle entry.
RB1 mutations cause retinoblastoma, a pediatric eye cancer, and are associated with osteosarcoma, small-cell lung cancer, and breast cancer. Drug development targeting the RB1 pathway includes CDK4/6 inhibitors (e.g., palbociclib), which block pRB phosphorylation, restoring its tumor-suppressive function in RB1-intact cancers, and improving outcomes in hormone receptor-positive breast cancer.