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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • el-Deiry, WS; Harper, JW; O'Connor, PM; Velculescu, VE; Canman, CE; Jackman, J; Pietenpol, JA; Burrell, M; Hill, DE; Wang, Y

Published Date

  • March 1994

Published In

Volume / Issue

  • 54 / 5

Start / End Page

  • 1169 - 1174

PubMed ID

  • 8118801

Pubmed Central ID

  • 8118801

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng