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p53 regulation by post-translational modification and nuclear retention in response to diverse stresses

Oncogene volume 18, pages 7656–7665 (1999)Cite this article

Abstract

p53 activation by diverse stresses involves post-translational modifications that alter its structure and result in its nuclear accumulation. We will discuss several unresolved topics regarding p53 regulation which are currently under investigation. DNA damage is perhaps the best-studied stress which activates p53, and recent data implicate phosphorylation at N-terminal serine residues as critical in this process. We discuss recent data regarding the potential kinases which modify p53 and the possible role of the resulting phosphorylation events. By contrast, much less is understood about agents which disrupt the mitotic spindle. The cell cycle phase, induction signal, and biochemical mechanism of the reversible arrest induced by microtubule disruption are currently under investigation. Finally, a key event in response to any genotoxic stress is the accumulation of p53 in the nucleus. The factors which determine the steady state level of p53 are starting to be elucidated, but the mechanisms responsible for nuclear accumulation and nuclear export remain controversial. We discuss new studies revealing a mechanism for nuclear retention of p53, and the potential contributions of MDM2 to this process.

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Acknowledgements

This work is supported by a postdoctoral fellowship from the NIH (to GS Jimenez), a National Science Foundation Graduate Fellowship (to JM Stommel), and grants from the NIH and the G Harold and Leila Y Mathers Charitable Foundation.

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  1. Gene Expression Laboratory, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, 92037, California, CA, USA

    Gretchen S Jimenez, Shireen H Khan, Jayne M Stommel & Geoffrey M Wahl

  2. Department of Biology, University of California at San Diego, La Jolla, 92037, California, CA, USA

    Shireen H Khan & Jayne M Stommel

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Jimenez, G., Khan, S., Stommel, J. et al. p53 regulation by post-translational modification and nuclear retention in response to diverse stresses. Oncogene 18, 7656–7665 (1999). https://doi.org/10.1038/sj.onc.1203013

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