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Science 292 (5523): 1910-1915

Copyright © 2001 by the American Association for the Advancement of Science

A p53 Amino-Terminal Nuclear Export Signal Inhibited by DNA Damage-Induced Phosphorylation

Yanping Zhang,* Yue Xiongdagger

The p53 protein is present in low amounts in normally growing cells and is activated in response to physiological insults. MDM2 regulates p53 either through inhibiting p53's transactivating function in the nucleus or by targeting p53 degradation in the cytoplasm. We identified a previously unknown nuclear export signal (NES) in the amino terminus of p53, spanning residues 11 to 27 and containing two serine residues phosphorylated after DNA damage, which was required for p53 nuclear export in colloboration with the carboxyl-terminal NES. Serine-15-phosphorylated p53 induced by ultraviolet irradiation was not exported. Thus, DNA damage-induced phosphorylation may achieve optimal p53 activation by inhibiting both MDM2 binding to, and the nuclear export of, p53.

Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, NC 27599-7295, USA.
*   Present address: Department of Molecular and Cellular Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.

dagger    To whom correspondence should be addressed. E-mail: yxiong{at}email.unc.edu

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Interferon regulatory factor-3 is an in vivo target of DNA-PK.
A. Y. Karpova, M. Trost, J. M. Murray, L. C. Cantley, and P. M. Howley (2002)
PNAS 99, 2818-2823
   Abstract »    Full Text »    PDF »
Requirement of ATM in UVA-induced Signaling and Apoptosis.
Y. Zhang, W.-Y. Ma, A. Kaji, A. M. Bode, and Z. Dong (2002)
J. Biol. Chem. 277, 3124-3131
   Abstract »    Full Text »    PDF »
C-Terminal Ubiquitination of p53 Contributes to Nuclear Export.
M. A. E. Lohrum, D. B. Woods, R. L. Ludwig, E. Balint, and K. H. Vousden (2001)
Mol. Cell. Biol. 21, 8521-8532
   Abstract »    Full Text »    PDF »
Dual Role of p300 in the Regulation of p53 Stability.
H. Kawai, L. Nie, D. Wiederschain, and Z.-M. Yuan (2001)
J. Biol. Chem. 276, 45928-45932
   Abstract »    Full Text »    PDF »
MOLECULAR BIOLOGY: Getting p53 Out of the Nucleus.
V. Gottifredi and C. Prives (2001)
Science 292, 1851-1852
   Full Text »
Interferon regulatory factor-3 is an in vivo target of DNA-PK.
A. Y. Karpova, M. Trost, J. M. Murray, L. C. Cantley, and P. M. Howley (2002)
PNAS 99, 2818-2823
   Abstract »    Full Text »    PDF »

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