Ioana Ferecatu^1,2, Vincent Rincheval^1,2, Bernard Mignotte^1,2, Jean-Luc Vayssiere^1,2

1Laboratoire de Genetique et Biologie Cellulaire, CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, 45 avenue des Etats-Unis, 78035 Versailles cedex, France,²Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, 45 avenue des Etats-Unis, 78035 Versailles cedex, France

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Stressors Which Activate p53

4. p53 localization in stressed and unstressed cells

4.1. Nuclear Localization

4.2. Mitochondrial Localization

4.3. Other Locations

5. Post-Translational Modifications Of p53

5.1. Phosphorylation

5.2. Acetylation

5.3. Ubiquitination

5.4. Other Modifications

6. Regulation Of p53 Location By Post-Translational Modifications

6.1. Post-translational modifications in nuclear import-export regulation

6.2. Post-translational modifications in mitochondrial targeting

7. Concluding Remarks

8. Acknowledgements

9. References

1. ABSTRACT

A broad range of stressors - intrinsic and extrinsic to the cell - stabilize and activate p53, affecting it by a series of post-translational modifications such as phosphorylation, acetylation, ubiquitination, methylation and sumoylation. p53 is able to integrate each kind of post-translational modification and to adequately respond by inducing cell cycle arrest, senescence or apoptosis. p53 controls the cell fate at the level of different compartments, and its trafficking among organelles is modulated by different types of post-translational modifications. Thus, miss-location or sequestration of p53 within a compartment might obstruct its function as tumor suppressor leading to cell immortalization and tumorigenesis. The aim of this contribution is to give a unified overview of several reports in the literature, concerning the post-translational modifications endured by p53 which regulate its cellular trafficking and distribution at different organelles.