PMID- 10425208 OWN - NLM STAT- MEDLINE DCOM- 19990908 LR - 20161124 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 261 IP - 2 DP - 1999 Aug 2 TI - The p38MAPK inhibitor SB203580 alleviates ultraviolet-induced phosphorylation at serine 389 but not serine 15 and activation of p53. PG - 464-71 AB - 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. CI - Copyright 1999 Academic Press. FAU - Keller, D AU - Keller D AD - 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. FAU - Zeng, X AU - Zeng X FAU - Li, X AU - Li X FAU - Kapoor, M AU - Kapoor M FAU - Iordanov, M S AU - Iordanov MS FAU - Taya, Y AU - Taya Y FAU - Lozano, G AU - Lozano G FAU - Magun, B AU - Magun B FAU - Lu, H AU - Lu H LA - eng GR - CA-39360/CA/NCI NIH HHS/United States GR - ES-08456/ES/NIEHS NIH HHS/United States GR - R01 CA 79721/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Enzyme Inhibitors) RN - 0 (Imidazoles) RN - 0 (Pyridines) RN - 0 (Tumor Suppressor Protein p53) RN - 452VLY9402 (Serine) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - OU13V1EYWQ (SB 203580) SB - IM MH - Animals MH - Apoptosis/drug effects/radiation effects MH - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/metabolism MH - Enzyme Inhibitors/*pharmacology MH - Humans MH - Imidazoles/*pharmacology MH - In Vitro Techniques MH - Male MH - Mice MH - *Mitogen-Activated Protein Kinases MH - Phosphorylation MH - Pyridines/*pharmacology MH - Serine/chemistry MH - Testicular Neoplasms/enzymology MH - Transcription, Genetic/drug effects/radiation effects MH - Tumor Cells, Cultured MH - Tumor Suppressor Protein p53/chemistry/*metabolism/*radiation effects MH - Ultraviolet Rays MH - p38 Mitogen-Activated Protein Kinases EDAT- 1999/07/30 00:00 MHDA- 1999/07/30 00:01 CRDT- 1999/07/30 00:00 PHST- 1999/07/30 00:00 [pubmed] PHST- 1999/07/30 00:01 [medline] PHST- 1999/07/30 00:00 [entrez] AID - 10.1006/bbrc.1999.1023 [doi] AID - S0006-291X(99)91023-9 [pii] PST - ppublish SO - Biochem Biophys Res Commun. 1999 Aug 2;261(2):464-71. doi: 10.1006/bbrc.1999.1023.