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Mol Cell Biol, March 1998, p. 1400-1407, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

p53-Dependent Elevation of p21Waf1 Expression by UV Light Is Mediated through mRNA Stabilization and Involves a Vanadate-Sensitive Regulatory System

Myriam Gorospe, Xiantao Wang, and Nikki J. Holbrook*

Section on Gene Expression and Aging, Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224

Received 21 July 1997/Returned for modification 27 August 1997/Accepted 21 November 1997

Exposure of mammalian cells to adverse stimuli triggers the expression of numerous stress response genes, many of which are presumed to enhance cell survival. In this study, we examined the mechanisms contributing to the induction of p21Waf1 by stress and its influence on the survival of cells subjected to short-wavelength UVC irradiation. UVC was found to elevate p21Waf1 mRNA expression in mouse embryonal fibroblasts (MEFs) and human colorectal carcinoma (RKO) cells in a p53-dependent manner. The lack of p21Waf1 induction in p53-deficient MEFs and RKO cells correlated with diminished cell survival following UVC irradiation. Unexpectedly, UVC treatment was also found to block the induction of p21Waf1 by various stress-inducing agents such as mimosine in the p53-deficient cells. Additional studies indicated that induction of p21Waf1 by UVC occurs primarily through enhanced mRNA stability rather than increased transcription; in p53-/- MEFs, failure to elevate p21Waf1 after treatment with UVC appears to be due to their inability to stabilize the p21Waf1 transcripts. Treatment of the p53-/- MEFs with the protein tyrosine phosphatase inhibitor vanadate reversed the UVC-induced block on p21Waf1 induction and resulted in their enhanced survival following irradiation. Thus, in cells bearing normal p53, UVC augments p21Waf1 expression by increasing the half-life of p21Waf1 mRNA; without p53, p21Waf1 mRNA remains unstable after UVC, apparently due to a pathway involving tyrosine phosphatase activity.

* Corresponding author. Mailing address: Box 12, Section on Gene Expression and Aging, Laboratory of Biological Chemistry, National Institutes of Health, National Institute on Aging, GRC, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825. Phone: (410) 558-8197. Fax: (410) 558-8335. E-mail: nikki-holbrook{at}nih.gov.




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