Retinoblastoma protein family (RB family)

The Retinoblastoma (RB) protein family, which includes RB1, RBL1 (p107), and RBL2 (p130), serves as a fundamental regulator of the mammalian cell cycle by controlling the G1/S phase transition (UniProt, 2024). These 'pocket proteins' function by sequestering E2F transcription factors, thereby suppressing the expression of genes necessary for DNA synthesis and cell cycle progression (PubMed, 2021). In many cancers, the RB pathway is disrupted either through direct mutations in the RB1 gene or through the overactivation of upstream kinases like CDK4 and CDK6, which hyperphosphorylate and inactivate RB (NIH, 2023). Consequently, the RB family is a central focus in oncology, particularly for the application of CDK4/6 inhibitors such as palbociclib and abemaciclib, which aim to restore RB-mediated cell cycle arrest (StatPearls, 2023). However, the loss of RB1 function is a well-documented mechanism of resistance to these therapies, highlighting its importance as both a therapeutic node and a predictive biomarker (PubMed, 2022).

Other names

RB1p107p130Pocket proteinsRetinoblastoma-associated proteinRBL1RBL2

Drugs targeting the RB pathway, primarily CDK4/6 inhibitors, work by preventing the phosphorylation of RB family members. This keeps the proteins in a hypophosphorylated, active state where they bind to E2F transcription factors, effectively blocking the transition from G1 to S phase and inhibiting tumor cell proliferation (StatPearls, 2023; PubMed, 2021).