WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis

Cancer Res. 1994 Mar 1;54(5):1169-74.


The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Apoptosis / physiology*
  • Cell Nucleus / physiology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA Damage
  • G1 Phase / physiology*
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, p53 / genetics
  • Genes, p53 / physiology
  • Humans
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / pathology
  • Mice
  • Mutation / genetics
  • Protein Kinase Inhibitors*
  • Protein Kinases / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / physiology*


  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Protein Kinase Inhibitors
  • Tumor Suppressor Protein p53
  • Protein Kinases