CDK4, Unactive

CDK4 is a member of the cyclin-dependent protein kinases and is involved in the control of cell proliferation during the G1 phase of the cell cycle. CDK4 forms a complex with the D-type cyclins which regulate its activity. CDK4 is inhibited by p16, also known as cyclin-dependent kinase inhibitor-2. CDK4 can mediate phosphorylation of the C-terminal region of RB protein leading to an active transcriptional repression of E2F complex (1). CDC37 and HSP90 can preferentially associate with the fraction of CDK4 not bound to D-type cyclins. Pharmacologic inactivation of CDC37/HSP90 function leads to reduced stability of CDK4. SMAD3 is a major physiologic substrate of the G1 cyclin-dependent kinases CDK4 and CDK2 (2).