title: Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation.
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 gamma 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 gamma 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, gamma 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 gamma radiation.
authors.affiliation: Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kapoor
authors.forename: G
authors.initials: G
authors.lastname: Lozano
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D047390:Casein Kinase II; D002478:Cells, Cultured; D004249:DNA Damage / Q000502:physiology*; D005720:Gamma Rays; D010766:Phosphorylation; D011485:Protein Binding / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases