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First published online 25 November 2008
doi: 10.1242/jcs.030098

Journal of Cell Science 121, 4098-4105 (2008)
Published by The Company of Biologists 2008
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Research Article

p53 is localized to a sub-nucleolar compartment after proteasomal inhibition in an energy-dependent manner

Orit Karni-Schmidt1,2, Andrew Zupnick1, Mirela Castillo2, Aqeel Ahmed2, Tulio Matos2, Philippe Bouvet3, Carlos Cordon-Cardo2 and Carol Prives1,*

1 Department of Biological Sciences, Columbia University, New York, NY 10027, USA
2 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
3 Laboratoire de Biologie Moléculaire de la Cellule, UMR 5161, Ecole Normale Supérieure de Lyon 46, Allée d'Italie, 69364 Lyon, Cedex 07, France

* Author for correspondence (e-mail: clp3{at}columbia.edu)

Accepted 17 August 2008

The tumor suppressor p53 is activated in response to many forms of cellular stress leading to cell cycle arrest, senescence or apoptosis. Appropriate sub-cellular localization is essential for modulating p53 function. We recently showed that p53 localizes to the nucleolus after proteasome inhibition with MG132 and this localization requires sequences within its carboxyl terminus. In the present study, we found that after treatment with MG132, p53 associates with a discrete sub-nucleolar component, the fibrillar center (FC), a region mainly enriched with RNA polymerase I. Moreover, we now demonstrate that this localization is an energy-dependent process as reduction of ATP levels prevents nucleolar localization. In addition, p53 sub-nucleolar accumulation is abolished when cells are subjected to various types of genotoxic stress. Furthermore, we show that monoubiquitination of p53, which causes it to localize to the cytoplasm and nucleoplasm, does not prevent the association of p53 with the nucleolus after MG132 treatment. Importantly, we demonstrate that p53 nucleolar association occurs in lung and bladder carcinomas.

Key words: p53, Nucleolus, DNA damage, NoLS, Fibrillar center (FC), Dense fibrillar center (DFC), Ubiquitin


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