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The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has
been implicated in the control of the G1 to S phase transition in mammals. To
identify potential Cdk2 regulators, we have employed an improved two-hybrid
system to isolate human genes encoding Cdk-interacting proteins (Cips). CIP1
encodes a novel 21 kd protein that is found in cyclin A, cyclin D1, cyclin E,
and Cdk2 immunoprecipitates. p21CIP1 is a potent, tight-binding inhibitor of
Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2, cyclin E-Cdk2,
cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Cotransfection experiments
indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner
to control cell cycle progression.
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