Overview:

CDK4 is a member of the cyclin-dependent protein kinase family and is involved in the control of cell proliferation during the G1 phase of cell cycle. CDK4 forms a complex with the D-type cyclins and is inhibited by p16 (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. SMAD3 is a major physiologic substrate of the G1 cyclin-dependent kinases CDK4 and CDK2 (2).

References:

1. Harbour, J W. et al: Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98: 859-869, 1999. 

2. Matsuura, I. et al: Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 430: 226-231, 2004.