WAF1/CIP1 Is Induced in p53-mediated G1 Arrest and Apoptosis

Wafik S. El-Deiry, Victor E. Velculescu, Christine E. Canman, Jennifer A. Pietenpol, Michael B. Kastan, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1169-1174
Number of pages6
JournalCancer Research
Volume54
Issue number5
StatePublished - Mar 15 1994

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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