The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases

Cell. 1993 Nov 19;75(4):805-16. doi: 10.1016/0092-8674(93)90499-g.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Polyomavirus Transforming / metabolism
  • Base Sequence
  • CDC2-CDC28 Kinases*
  • Cell Cycle*
  • Cloning, Molecular / methods
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases*
  • Cyclins / antagonists & inhibitors*
  • Cyclins / physiology*
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Kinase Inhibitors*
  • Protein-Serine-Threonine Kinases*
  • Recombinant Proteins
  • Retinoblastoma Protein / metabolism

Substances

  • Antigens, Polyomavirus Transforming
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Protein Kinase Inhibitors
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases

Associated data

  • GENBANK/L20888
  • GENBANK/L20889
  • GENBANK/L22499
  • GENBANK/L25610
  • GENBANK/L26083
  • GENBANK/L33709
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924
  • GENBANK/U00968