CDK4 and neoplasm: Specifically, CDK4 activity is restricted to the G1–S phase transition and is controlled as follows: (1) positively by its association with regulatory cyclin D subunits (D1, D2, and D3), and (2) negatively by tumor suppressors such as p16INK4A encoded by CDKN2A, which prevents the interaction of CDK4 with cyclin Ds [63].