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  • Original Paper
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Nuclear accumulation of p53 following inhibition of transcription is not due to diminished levels of MDM2

Oncogene volume 23, pages 5505–5512 (2004)Cite this article

Abstract

A common mechanism by which the tumor suppressor p53 accumulates in the nucleus following cellular stress is through the attenuation of its interaction with MDM2, a protein involved in the nuclear export and degradation of p53. This is accomplished by induced modifications of p53, MDM2 or both. We have previously found that the kinase and mRNA synthesis inhibitor DRB (5,6-dichloro-1-b-D-ribofuranosylbenzimidazole) induces the nuclear accumulation of p53 without concomitant phosphorylation of the ser15 site of p53, which is thought to be a modification important for the attenuation of p53–MDM2 interaction. It has been proposed that the mechanism by which p53 accumulates following blockage of transcription involves the downregulation of MDM2 expression. In this study, we tested this hypothesis and found that after DRB treatment, p53 accumulated despite the fact that MDM2 levels remained high in human cells. Furthermore, over expression of MDM2 did not prevent the accumulation of p53 following DRB treatment. In, addition, p53 accumulating in the nucleus after DRB treatment was able to interact with MDM2 and was ubiquitylated. These findings suggest that blockage of transcription induce the nuclear accumulation of p53 without breaking the p53–MDM2 regulation loop.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (CA-82376) and from funds from the University of Michigan Cancer Biology Training Program and Rackham Graduate School.

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Authors and Affiliations

  1. Department of Radiation Oncology, Division of Radiation and Cancer Biology, Program in Molecular and Cellular Biology, University of Michigan Medical School, Ann Arbor, 48109-0936, MI, USA

    Heather M O'Hagan & Mats Ljungman

  2. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, 48109-0936, MI, USA

    Mats Ljungman

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Correspondence to Mats Ljungman.

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O'Hagan, H., Ljungman, M. Nuclear accumulation of p53 following inhibition of transcription is not due to diminished levels of MDM2. Oncogene 23, 5505–5512 (2004). https://doi.org/10.1038/sj.onc.1207709

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