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Paper Title

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

Authors

Bert Vogelstein
Bert Vogelstein
Kenneth W. Kinzler
Kenneth W. Kinzler
Michael Barry Kastan
Michael Barry Kastan
Stephen J. Elledge
Stephen J. Elledge
Kurt W. Kohn
Kurt W. Kohn

Article Type

Research Article

Issue

Volume : 54 | Issue : 5 | Page No : 1169–1174

Published On

January, 1994

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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.

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