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Science 302 (5652): 1972-1975

Copyright © 2003 by the American Association for the Advancement of Science

Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2

Muyang Li, Christopher L. Brooks, Foon Wu-Baer, Delin Chen, Richard Baer, Wei Gu*

Abstract: Although Mdm2-mediated ubiquitination is essential for both degradation and nuclear export of p53, the molecular basis for the differential effects of Mdm2 remains unknown. Here we show that low levels of Mdm2 activity induce monoubiquitination and nuclear export of p53, whereas high levels promote p53's polyubiquitination and nuclear degradation. A p53-ubiquitin fusion protein that mimics monoubiquitinated p53 was found to accumulate in the cytoplasm in an Mdm2-independent manner, indicating that monoubiquitination is critical for p53 trafficking. These results clarify the nature of ubiquitination-mediated p53 regulation and suggest that distinct mechanisms regulate p53 function in accordance with the levels of Mdm2 activity.

Institute for Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.

* To whom correspondence should be addressed. E-mail: wg8{at}columbia.edu


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   Abstract »    Full Text »    PDF »
Monoubiquitylation promotes mitochondrial p53 translocation.
N. D. Marchenko, S. Wolff, S. Erster, K. Becker, and U. M. Moll (2007)
EMBO J. 26, 923-934
   Abstract »    Full Text »    PDF »
CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery.
J.-M. Nam, Y. Onodera, Y. Mazaki, H. Miyoshi, S. Hashimoto, and H. Sabe (2007)
EMBO J. 26, 647-656
   Abstract »    Full Text »    PDF »
Cancer-Associated Mutations in the MDM2 Zinc Finger Domain Disrupt Ribosomal Protein Interaction and Attenuate MDM2-Induced p53 Degradation.
M. S. Lindstrom, A. Jin, C. Deisenroth, G. White Wolf, and Y. Zhang (2007)
Mol. Cell. Biol. 27, 1056-1068
   Abstract »    Full Text »    PDF »
FBXO11 Promotes the Neddylation of p53 and Inhibits Its Transcriptional Activity.
W. M. Abida, A. Nikolaev, W. Zhao, W. Zhang, and W. Gu (2007)
J. Biol. Chem. 282, 1797-1804
   Abstract »    Full Text »    PDF »
Outcomes of p53 activation - spoilt for choice.
K. H. Vousden (2006)
J. Cell Sci. 119, 5015-5020
   Abstract »    Full Text »    PDF »
Regulation of p53 Localization and Activity by Ubc13.
A. Laine, I. Topisirovic, D. Zhai, J. C. Reed, K. L. B. Borden, and Z. Ronai (2006)
Mol. Cell. Biol. 26, 8901-8913
   Abstract »    Full Text »    PDF »
MDM2 Is Required for Suppression of Apoptosis by Activated Akt1 in Salivary Acinar Cells.
K. H. Limesand, K. L. Schwertfeger, and S. M. Anderson (2006)
Mol. Cell. Biol. 26, 8840-8856
   Abstract »    Full Text »    PDF »
p53-Independent Induction of Rat Hepatic Mdm2 following Administration of Phenobarbital and Pregnenolone 16{alpha}-Carbonitrile.
D. M. Nelson, V. Bhaskaran, W. R. Foster, and L. D. Lehman-McKeeman (2006)
Toxicol. Sci. 94, 272-280
   Abstract »    Full Text »    PDF »
Posttranslational Modification and Cell Type-Specific Degradation of Varicella-Zoster Virus ORF29p.
C. L. Stallings and S. J. Silverstein (2006)
J. Virol. 80, 10836-10846
   Abstract »    Full Text »    PDF »

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