Retinoblastoma-associated protein (RB1) (RB1)

Retinoblastoma-associated protein (RB1) is a foundational tumor suppressor that acts as a gatekeeper of the G1/S phase transition in the eukaryotic cell cycle (UniProt P06400). It primarily functions by sequestering E2F transcription factors, thereby inhibiting the expression of genes necessary for DNA synthesis and cell cycle progression (PubMed: 25713293). The activity of RB1 is tightly regulated by its phosphorylation state; it is active when hypophosphorylated and inactivated when hyperphosphorylated by cyclin-dependent kinases (CDK4 and CDK6) in complex with D-type cyclins (NIH: Gene ID 5925). Loss of RB1 function through genetic mutation, deletion, or viral oncoprotein binding is a hallmark of various malignancies, including its namesake retinoblastoma, as well as osteosarcoma and small cell lung cancer (PubMed: 29474161). In modern oncology, RB1 serves as a critical determinant of sensitivity to CDK4/6 inhibitors, such as palbociclib and abemaciclib, which aim to maintain RB1 in its active, growth-suppressive state to halt tumor proliferation (PubMed: 30333316). However, the complete loss of RB1 is a frequent mechanism of acquired resistance to these therapies, making its status a vital biomarker in clinical decision-making (PubMed: 31515461).

Other names

pRbRBRetinoblastoma 1p105-RbPP110Retinoblastoma-associated protein 1

Inhibition of RB1 phosphorylation by CDK4/6 inhibitors to maintain the protein in its active, growth-suppressive hypophosphorylated state (PubMed: 30333316).