Since Rb’s C – terminal helix exclusively binds cyclin D-Cdk4,6 and not other cell cycle dependent cyclin-Cdk complexes, through experiments mutating this helix in HMEC cells,[16] it has been conclusively shown that the cyclin D – Rb interaction is critical in the following roles (1) promoting the G1/S transition (2) allowing Rb dissociation from chromatin, and (3) E2F1 activation.