RB1 and neoplasm: Both p15INK4b and p16INK4a bind to and inhibit CDK4 and CDK6, maintaining the growth-suppressive activity of the Rb tumor suppressor; loss or inactivation of either p15INK4b or p16INK4a contributes to the dysregulation of the CDK4/6-cyclin-Rb pathway and to the loss of cell-cycle control [71,72].