RB protein primarily functions as a
Hypophosphorylated Rb binds and represses E2F transcription factors, preventing expression of genes required for S-phase entry. Mitogenic signaling activates cyclin-D–CDK4/6 and cyclin-E–CDK2 complexes that progressively phosphorylate Rb. Hyperphosphorylated Rb releases E2F, allowing S-phase progression. Loss of Rb function therefore removes a critical G1 checkpoint and contributes to uncontrolled proliferation. Careful
Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)