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Science 12 December 2003:
Vol. 302. no. 5652, pp. 1972 - 1975
DOI: 10.1126/science.1091362
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Reports

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

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

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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R. K. Mishra, S. S. Jatiani, A. Kumar, V. R. Simhadri, R. V. Hosur, and R. Mittal (2004)
J. Biol. Chem. 279, 31445-31454
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Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways.
S. Hussain, J. B. Wilson, A. L. Medhurst, J. Hejna, E. Witt, S. Ananth, A. Davies, J.-Y. Masson, R. Moses, S. C. West, et al. (2004)
Hum. Mol. Genet. 13, 1241-1248
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The Targeting of the Proteasomal Regulatory Subunit S2 by Adenovirus E1A Causes Inhibition of Proteasomal Activity and Increased p53 Expression.
X. Zhang, A. S. Turnell, C. Gorbea, J. S. Mymryk, P. H. Gallimore, and R. J. A. Grand (2004)
J. Biol. Chem. 279, 25122-25133
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Wwp2, an E3 Ubiquitin Ligase That Targets Transcription Factor Oct-4 for Ubiquitination.
H. M. Xu, B. Liao, Q. J. Zhang, B. B. Wang, H. Li, X. M. Zhong, H. Z. Sheng, Y. X. Zhao, Y. M. Zhao, and Y. Jin (2004)
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