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  • Original Paper
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Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage

Oncogene volume 23, pages 49–57 (2004)Cite this article

Abstract

The p53 tumor suppressor protein plays a critical role in mediating cellular response to stress. Upon DNA damage, post-translational modifications stabilize and activate this nuclear phosphoprotein. To determine the effect of phosphorylation site mutants in the context of the whole p53 protein, we performed reporter assays in p53 and MDM2 knockout mouse embryonic fibroblasts transfected with full-length p53 constructs. We show that mutation of S37 causes a decrease in p53 transcriptional activity compared to wild-type p53. Our data further suggest that the dephosphorylation of p53 at S37 is a regulated event involving protein phosphatase 2A (PP2A). Coimmunoprecipitation and immunofluorescence microscopy studies demonstrate that PP2A and p53 associate with one another in vivo following γ-irradiation. Consistent with these observations, phosphorylated S37 accumulates in cell extracts prepared from γ-irradiated Molt-4 cells in the presence of okadaic acid. Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37. These results suggest that dephosphorylation of p53 at S37 plays a role in the transcriptional regulation of the p53 protein in response to DNA damage.

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Acknowledgements

We thank Michael Radonovich for preparation of γ-irradiated cells, Dr Tom Misteli for technical suggestions on image processing and Dr Cynthia Pise-Masison for helpful discussions. Microscopy images in this article were generated in the imaging facility of Tom Misteli and processed in the NIH, NCI Core Imaging Facility.

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Authors and Affiliations

  1. Basic Research Laboratory, Virus Tumor Biology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, MD, USA

    Kathleen M Dohoney, Claire Guillerm & John N Brady

  2. Advanced Technology Center, Center for Cancer Research, National Cancer Institute, Gaithersburg, 20892, MD, USA

    Craig Whiteford

  3. Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Md, USA

    Cem Elbi & Gordon L Hager

  4. Flinders University of South Australia School of Medicine, Bedford Park, 5042, South Australia, Australia

    Paul F Lambert

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  1. Kathleen M Dohoney
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Correspondence to John N Brady.

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Dohoney, K., Guillerm, C., Whiteford, C. et al. Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage. Oncogene 23, 49–57 (2004). https://doi.org/10.1038/sj.onc.1207005

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