title: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
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.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: J W
authors.initials: JW
authors.lastname: Harper
authors.forename: G R
authors.initials: GR
authors.lastname: Adami
authors.forename: N
authors.initials: N
authors.lastname: Wei
authors.forename: K
authors.initials: K
authors.lastname: Keyomarsi
authors.forename: S J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D003001:Cloning, Molecular / Q000379:methods; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases