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Regulating the p53 system through ubiquitination

Oncogene volume 23, pages 2096–2106 (2004)Cite this article

Abstract

The tumor suppressor p53 is tightly controlled at low levels in cells by constant ubiquitination and proteasomal degradation. In response to stresses, ubiquitination of p53 is inhibited through diverse pathways, depending on the nature of the stimulus and cell type. This leads to the accumulation and activation of p53, which induces cell cycle arrest and/or apoptosis to prevent cells from transformation. Many studies have indicated that defects of the p53 system are present in most, if not all, human tumor cells. Meanwhile, significant progress has been made in understanding the molecular mechanisms of p53 ubiquitination and the regulation of the p53 system. Therefore, it is possible now to consider targeting ubiquitination as a means to regulate and reactivate p53 in tumors. Emerging evidence suggests that inhibiting the E3 activity of Mdm2, blocking the interaction of p53 and Mdm2, and restoring the function of mutated p53 are potential effective strategies to kill certain tumor cells selectively. It is conceivable that new chemotherapeutic agents based on these studies will be generated in the not-so-distant future.

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Acknowledgements

We would like to thank Drs Mary Perry and Kevin Lorick for critical reading and editing of the manuscript. We apologize to colleagues whose important contributions have been cited only indirectly due to space limitation. This publication has been partially funded with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-CO-12400.

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  1. Regulation of Protein Function Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, 560/22-64, 1050 Boyles Street, Frederick, 21702, MD, USA

    Yili Yang & Allan M Weissman

  2. Laboratory of Cancer Prevention, SAIC-Frederick, National Cancer Institute-Frederick, National Institutes of Health, Frederick, 21702-1201, MD, USA

    Chou-Chi H Li

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Yang, Y., Li, CC. & Weissman, A. Regulating the p53 system through ubiquitination. Oncogene 23, 2096–2106 (2004). https://doi.org/10.1038/sj.onc.1207411

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