The p38MAPK inhibitor SB203580 alleviates ultraviolet-induced phosphorylation at serine 389 but not serine 15 and activation of p53.
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.
Keller
D
D
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.
Zeng
X
X
Li
X
X
Kapoor
M
M
Iordanov
M S
MS
Taya
Y
Y
Lozano
G
G
Magun
B
B
Lu
H
H
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
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