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Arginine methylation regulates the p53 response

Nature Cell Biology volume 10, pages 1431–1439 (2008)Cite this article

Abstract

Activation of the p53 tumour suppressor protein in response to DNA damage leads to apoptosis or cell-cycle arrest. Enzymatic modifications are widely believed to affect and regulate p53 activity. We describe here a level of post-translational control that has an important functional consequence on the p53 response. We show that the protein arginine methyltransferase (PRMT) 5, as a co-factor in a DNA damage responsive co-activator complex that interacts with p53, is responsible for methylating p53. Arginine methylation is regulated during the p53 response and affects the target gene specificity of p53. Furthermore, PRMT5 depletion triggers p53-dependent apoptosis. Thus, methylation on arginine residues is an underlying mechanism of control during the p53 response.

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Figure 1: PRMT5 binds to the p53 co-factor Strap.
Figure 2: PRMT5 and Strap interact in cells.
Figure 3: PRMT5 regulates p53 activity.
Figure 4: p53 is physiologically methylated on arginine residues.
Figure 5: p53 arginine methylation in cells.
Figure 6: PRMT5 and the p53 response.
Figure 7: PRMT5 influences the functional properties of p53.

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Acknowledgements

We thank the MRC, Cancer Research UK, EU, LRF and AICR for supporting this work, and Rosemary Williams for assistance in preparing the manuscript.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Medical Sciences Division, Laboratory of Cancer Biology, University of Oxford, Old Road Campus Research Building, Old Road Campus, off Roosevelt Drive, OX3 7DQ, Oxford, UK

    Martin Jansson, Stephen T. Durant, Er-Chieh Cho, Sharon Sheahan & Nicholas B. La Thangue

  2. Nuffield Department of Clinical Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, OX3 7BN, Oxford, UK

    Mariola Edelmann & Benedikt Kessler

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  1. Martin Jansson
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Contributions

M.J., S.T.D., E.C. and S.S. designed, performed and analysed the experiments; M.E. and B.K. performed and interpreted the mass spectrometry; N.B.L.T. analysed the data and wrote the manuscript.

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Correspondence to Nicholas B. La Thangue.

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The authors declare no competing financial interests.

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Jansson, M., Durant, S., Cho, EC. et al. Arginine methylation regulates the p53 response. Nat Cell Biol 10, 1431–1439 (2008). https://doi.org/10.1038/ncb1802

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