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The interaction of p53 with the nuclear matrix is mediated by F-actin and modulated by DNA damage

Oncogene volume 21, pages 356–367 (2002)Cite this article

Abstract

The tumour suppressor protein p53 is localized in the cell nucleus where it serves to initiate cellular responses to a variety of stresses, particularly DNA damage and has the capacity to transactivate stress response genes. An emerging body of evidence indicates that its action is also exerted through direct protein–protein interactions. An approach to understanding p53 function has been to analyse its positioning in relation to nuclear structures and we have shown that p53 can associate with the nuclear matrix. A potential nuclear matrix component for this association is actin. Here we show that p53 interacts with nuclear F-actin and we map the domains involved in this interaction. Using fluorescence resonance energy transfer, we demonstrate that the partition of p53 between F-actin bound and unbound forms is not constant, but is modulated by the presence of DNA damage, which increases binding. Our results indicate that the dynamic interaction of p53 with the nuclear matrix has to be considered for a full understanding of the mechanisms of the p53-mediated cellular response to DNA damage.

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Acknowledgements

This work was supported by a Yorkshire Cancer Research program grant to J Milner.

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Authors and Affiliations

  1. Department of Biology, YCR P53 Research Group, University of York, York, YO10 5DD, UK

    Andrei L Okorokov, Carlos P Rubbi & Jo Milner

  2. Department of Surgery, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Su Metcalfe

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  1. Andrei L Okorokov
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  2. Carlos P Rubbi
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  3. Su Metcalfe
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  4. Jo Milner
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Correspondence to Jo Milner.

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Okorokov, A., Rubbi, C., Metcalfe, S. et al. The interaction of p53 with the nuclear matrix is mediated by F-actin and modulated by DNA damage. Oncogene 21, 356–367 (2002). https://doi.org/10.1038/sj.onc.1205112

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