Cyclin D-Cdk4,6 drives cell cycle progression via the retinoblastoma protein's C-terminal helix

摘要: The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein, Rb, which inhibits cycle progression until its inactivation by phosphorylation. However, role phosphorylation Rb in unclear because can be phosphorylated other cyclin-Cdk have targets that may division. Here, we show docks one side an alpha-helix C-terminus not recognized E, A, B. This helix-based docking mechanism shared p107 p130 Rb-family members across metazoans. Mutation C-terminal helix prevents phosphorylation, promotes G1 arrest, enhances Rb's tumor suppressive function. Our work conclusively demonstrates D-Rb interaction drives division defines a new class cyclin-based mechanisms.