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Originally published In Press as doi:10.1074/jbc.M007955200 on February 1, 2001

J. Biol. Chem., Vol. 276, Issue 17, 13852-13857, April 27, 2001
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Stabilization and Activation of p53 by the Coactivator Protein TAFII31*

Thomas BuschmannDagger , Yahong Lin§, Nadia Aithmitti§, Serge Y. FuchsDagger , Hua Lu||, Lois Resnick-SilvermanDagger , James J. ManfrediDagger , Ze'ev RonaiDagger , and Xiangwei Wu§**

From the Dagger  Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, the  Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon 97201, and the § Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Regulation of the stability of p53 is key to its tumor-suppressing activities. mdm2 directly binds to the amino-terminal region of p53 and targets it for degradation through the ubiquitin-proteasome pathway. The coactivator protein TAFII31 binds to p53 at the amino-terminal region that is also required for interaction with mdm2. In this report, we demonstrate that expression of TAFII31 inhibits mdm2-mediated ubiquitination of p53 and increases p53 levels. TAFII31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. UV-induced stabilization of p53 coincides with an increase in p53-associated TAFII31 and a corresponding decrease in mdm2-p53 interaction. Non-p53 binding mutant of TAFII31 fails to stabilize p53. Our results suggest that direct interaction of TAFII31 and p53 not only mediates p53 transcriptional activation but also protects p53 from mdm2-mediated degradation, thereby resulting in activation of p53 functions.

* This work was supported by a NCI, National Institutes of Health Grants P01 CA80058 (to Z. R. and X. W.), CA78419 (to Z. R.), and CA 69161 (to J. J. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| Supported by National Institutes of Health and American Cancer Society funds.

** To whom correspondence should be addressed: The Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. E-mail: xiangwei@ bcm.tmc.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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