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p53 binds the nuclear matrix in normal cells: binding involves the proline-rich domain of p53 and increases following genotoxic stress

Oncogene volume 20, pages 5449–5458 (2001)Cite this article

Abstract

The tumour suppressor p53 is a multifunctional protein important for the maintenance of genomic integrity. It is able to form molecular complexes with different DNA targets and also with cellular proteins involved in DNA transcription and DNA repair. In mammalian cells the biochemical processing of DNA occurs on a nuclear sub-structure termed the nuclear matrix. Previously Deppert and co-workers have identified p53 in association with the nuclear matrix in viral- and non-viral transformed cell lines. In the present study we demonstrate, for the first time, that p53 is bound to the nuclear matrix in primary cultures of normal mammalian cells and that this binding increases following DNA damage. Analysis of cell lines expressing structural mutants of p53 revealed that association with the nuclear matrix is independent of the tertiary and quaternary structure of p53. However, the proline-rich domain towards the N-terminus of p53 (residues 67 to 98) appeared important for binding to the nuclear matrix. This was demonstrated by TET-ON regulated expression of p53-derived constructs in p53−/− murine embryonic fibroblasts (MEF p53−/−). The proline-rich domain of p53 has potential for SH3 protein–protein interaction, and has a role in p53-mediated apoptosis and possibly base excision repair of DNA damage. We discuss our observations in relation to the ability of p53 to facilitate DNA repair and also review evidence indicating that matrix-bound p53 in SV40-transformed cells may facilitate the transforming potential of SV40 large T antigen.

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Acknowledgements

We thank Larry Donehower for kindly donating MEF p53−/− cells, Lorna Warnock for reading the manuscript and Julie Wainwright for help in its preparation. T Axe was a Gordon Piller Research Student funded by the Leukaemia Research Fund. This work was funded by programme and project grants from Yorkshire Cancer Research and the Leukaemia Research Fund to J Milner.

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  1. Ming Jiang & Tracy Axe

    Present address: Department of Surgery, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, UK

Authors and Affiliations

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

    Ming Jiang, Tracy Axe, Robert Holgate, Carlos P Rubbi, Andrei L Okorokov, Trevor Mee & Jo Milner

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Correspondence to Jo Milner.

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Jiang, M., Axe, T., Holgate, R. et al. p53 binds the nuclear matrix in normal cells: binding involves the proline-rich domain of p53 and increases following genotoxic stress. Oncogene 20, 5449–5458 (2001). https://doi.org/10.1038/sj.onc.1204705

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