title: The p38MAPK inhibitor SB203580 alleviates ultraviolet-induced phosphorylation at serine 389 but not serine 15 and activation of p53.
abstract: Phosphorylation of p53 at serine 389 has been shown to be responsive uniquely to UV but not gamma irradiation. This report describes identification of the UV-responsive p38MAPK protein as a serine 389 kinase. The immunoprecipitated p38MAPK from UV-irradiated murine embryonic testicular carcinoma F9 cells phosphorylated the serine 392 residue but not serine 15 of the human p53 protein in vitro and this phosphorylation was inhibited by a p38MAPK-specific chemical inhibitor SB203580. The inhibitor also remarkably alleviated the UV-caused induction and serine 389 but not serine 15 phosphorylation of the murine p53 protein in vivo. Subsequently, this compound suppressed transcriptional activity of p53 and partially retarded UV-induced apoptosis. Moreover, p53 bound to p38 as revealed by immunoprecipitation with anti-p53 antibodies from UV-treated F9 cells. Thus, these results suggest that UV-stimulated p53 phosphorylation at serine 389 is mediated by the stress-responsive p38MAPK.
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Cell and Development Biology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97201, USA.
authors.forename: D
authors.initials: D
authors.lastname: Keller
authors.forename: X
authors.initials: X
authors.lastname: Zeng
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Kapoor
authors.forename: M S
authors.initials: MS
authors.lastname: Iordanov
authors.forename: Y
authors.initials: Y
authors.lastname: Taya
authors.forename: G
authors.initials: G
authors.lastname: Lozano
authors.forename: B
authors.initials: B
authors.lastname: Magun
authors.forename: H
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology*; D012694:Serine / Q000737:chemistry; D013736:Testicular Neoplasms / Q000201:enzymology; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D016159:Tumor Suppressor Protein p53; D012694:Serine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580