Energy-dependent nucleolar localization of p53 in vitro requires two discrete regions within the p53 carboxyl terminus

O. Karni-Schmidt, A. Friedler, A. Zupnick, K. McKinney, M. Mattia, R. Beckerman, P. Bouvet, M. Sheetz, A. Fersht, C. Prives*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The p53 tumor suppressor is a nucleocytoplasmic shuttling protein that is found predominantly in the nucleus of cells. In addition to mutation, abnormal p53 cellular localization is one of the mechanisms that inactivate p53 function. To further understand features of p53 that contribute to the regulation of its trafficking within the cell, we analysed the subnuclear localization of wild-type and mutant p53 in human cells that were either permeabilized with detergent or treated with the proteasome inhibitor MG132. We, here, show that either endogenously expressed or exogenously added p53 protein localizes to the nucleolus in detergent-permeabilized cells in a concentration- and ATP hydrolysis-dependent manner. Two discrete regions within the carboxyl terminus of p53 are essential for nucleolar localization in permeabilized cells. Similarly, localization of p53 to the nucleolus after proteasome inhibition in unpermeabilized cells requires sequences within the carboxyl terminus of p53. Interestingly, genotoxic stress markedly decreases the association of p53 with the nucleolus, and phosphorylation of p53 at S392, a site that is modified by such stress, partially impairs its nucleolar localization. The possible significance of these findings is discussed.

Original languageAmerican English
Pages (from-to)3878-3891
Number of pages14
Issue number26
StatePublished - 31 May 2007

Bibliographical note

Funding Information:
We are particularly grateful to V Gottifredi and K De Vos for guidance during the earlier stages of this work. Thanks to J Ahn, N Baptiste, JC Bulinsky, M Poyurovsky, RPT Tanaka and M Urist for advice and help and to E Freulich who provided expert technical assistance. This work was supported by NIH Grants CA58316 and CA87497.


  • DNA damage
  • NoLS
  • Nucleolus
  • p53


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