What happens if the Rb protein is mutated and cannot be phosphorylated?
Retinoblastoma protein Rb functions as central gatekeeper integrating mitogenic signaling with E2F transcription program controlling G1/S restriction point. In quiescent or early G1 cells, Rb exists in hypophosphorylated state, binding E2F1, E2F2, E2F3 through pocket domains A and B, simultaneously recruiting histone deacetylases, SWI/SNF chromatin remodelers, and Polycomb complexes to repress promoters of cyclin E, cyclin A, thymidine kinase, dihydrofolate reductase, and DNA polymerase subunits. Mitogens induce cyclin D-CDK4/6 synthesis downstream of Ras-MAPK and PI3K pathways, which initiate
Ref: Weinberg, Biology of Cancer, 2nd ed., Chapter 8: Rb Pathway. NCBI Bookshelf: Cell Cycle Control.
