DOI: 10.1073/pnas.95.6.2834. Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation

Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation

10.1073/pnas.95.6.2834

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The tumor suppressor p53 is a nuclear phosphoprotein in which DNA-binding activity is increased on exposure to DNA-damaging agents such as UV or γ radiation by unknown mechanisms. Because phosphorylation of p53 at the casein kinase (CK) II site activates p53 for DNA-binding function in vitro , we sought to determine the in vivo relevance of phosphorylation at this site after UV and γ radiation. A polyclonal antibody was generated that binds to bacterially expressed p53 only when phosphorylated in vitro by CK II. Using this antibody, we showed that p53 is phosphorylated at the CK II site upon UV treatment of early passage rat embryo fibroblasts and RKO cells. In addition, DNA-binding assays indicated that phosphorylated p53 bound to a p53-responsive element, suggesting functional activation. However, γ radiation, which also stabilizes p53, did not result in phosphorylation at the CK II site. These results indicate that phosphorylation at the CK II site is one of the post-translational mechanisms through which p53 is activated in response to UV radiation and that different mechanisms activate p53 after DNA damage by γ radiation.

Bibliography

Kapoor, M., & Lozano, G. (1998). Functional activation of p53 via phosphorylation following DNA damage by UV but not Î³ radiation. Proceedings of the National Academy of Sciences, 95(6), 2834â2837.

Authors 2

Mini Kapoor (first)
Guillermina Lozano (additional)

References 34 Referenced 167

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:19 p.m.)
Indexed	1 week ago (Aug. 22, 2025, 12:45 a.m.)
Issued	27 years, 5 months ago (March 17, 1998)
Published	27 years, 5 months ago (March 17, 1998)
Published Online	27 years, 5 months ago (March 17, 1998)
Published Print	27 years, 5 months ago (March 17, 1998)

Funders 0

None

BibTeX

@article{Kapoor_1998, title={Functional activation of p53 via phosphorylation following DNA damage by UV but not γ radiation}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.6.2834}, DOI={10.1073/pnas.95.6.2834}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Kapoor, Mini and Lozano, Guillermina}, year={1998}, month=mar, pages={2834–2837} }

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  "abstract": "<jats:p>\n            The tumor suppressor p53 is a nuclear phosphoprotein in which DNA-binding activity is increased on exposure to DNA-damaging agents such as UV or \u03b3 radiation by unknown mechanisms. Because phosphorylation of p53 at the casein kinase (CK) II site activates p53 for DNA-binding function\n            <jats:italic>in vitro</jats:italic>\n            , we sought to determine the\n            <jats:italic>in vivo</jats:italic>\n            relevance of phosphorylation at this site after UV and \u03b3 radiation. A polyclonal antibody was generated that binds to bacterially expressed p53 only when phosphorylated\n            <jats:italic>in vitro</jats:italic>\n            by CK II. Using this antibody, we showed that p53 is phosphorylated at the CK II site upon UV treatment of early passage rat embryo fibroblasts and RKO cells. In addition, DNA-binding assays indicated that phosphorylated p53 bound to a p53-responsive element, suggesting functional activation. However, \u03b3 radiation, which also stabilizes p53, did not result in phosphorylation at the CK II site. These results indicate that phosphorylation at the CK II site is one of the post-translational mechanisms through which p53 is activated in response to UV radiation and that different mechanisms activate p53 after DNA damage by \u03b3 radiation.\n          </jats:p>",
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