Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Antigens, Polyomavirus Transforming / metabolism
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Base Sequence
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CDC2-CDC28 Kinases*
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Cell Cycle*
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Cloning, Molecular / methods
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases*
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Cyclins / antagonists & inhibitors*
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Cyclins / physiology*
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Humans
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Molecular Sequence Data
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Phosphorylation
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Protein Binding
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Protein Kinase Inhibitors*
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Protein Serine-Threonine Kinases*
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Recombinant Proteins
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Retinoblastoma Protein / metabolism
Substances
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Antigens, Polyomavirus Transforming
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Protein Kinase Inhibitors
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Recombinant Proteins
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Retinoblastoma Protein
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases
Associated data
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GENBANK/L20888
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GENBANK/L20889
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GENBANK/L22499
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GENBANK/L25610
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GENBANK/L26083
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GENBANK/L33709
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GENBANK/S60904
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GENBANK/S60905
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GENBANK/S60924
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GENBANK/U00968