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  • Original Paper
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Phosphorylation of p53 protein in response to ionizing radiation occurs at multiple sites in both normal and DNA-PK deficient cells

Oncogene volume 18, pages 1521–1527 (1999)Cite this article

Abstract

The tumour suppressor gene product, p53, is involved in mediating cellular responses to DNA damage including growth arrest and/or apoptosis. The mechanism by which p53 protein senses the presence of damaged DNA is not understood. The possibility that p53 may be post-translationally modified by enzymes that are activated in response to DNA damage including DNA-dependent protein kinase (DNA-PK), poly(ADP-ribose) polymerase and stress activated protein kinase has received considerable attention. Recent studies have indicated that DNA-PK is not required for the transactivation or apoptosis-promoting activities of p53 protein. However, the possibility that other functions of p53 may be dependent on phosphorylation by DNA-PK has not been explored. Here we describe a series of experiments that compares the expression, function and phosphorylation status of p53 protein in normal and DNA-PK-deficient scid cells. While several novel p53 phosphoforms are generated in response to DNA damage in normal cells, the same phosphoforms are observed in scid cells.

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Acknowledgements

We thank Dr Jim Woodgett for anti-GSK-3β antibodies and Dr Paul Fraser for anti-tau antibody. We are grateful to Drs Jim Woodgett, Norman Iscove and Gillian Wu for their advice and comments. This work was supported by the Medical Research Council of Canada and the National Cancer Institute of Canada.

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  1. Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Jacinth Abraham, David Spaner & Sam Benchimol

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  1. Jacinth Abraham
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Abraham, J., Spaner, D. & Benchimol, S. Phosphorylation of p53 protein in response to ionizing radiation occurs at multiple sites in both normal and DNA-PK deficient cells. Oncogene 18, 1521–1527 (1999). https://doi.org/10.1038/sj.onc.1202454

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