The p38MAPK inhibitor SB203580 alleviates ultraviolet-induced phosphorylation at serine 389 but not serine 15 and activation of p53

Biochem Biophys Res Commun. 1999 Aug 2;261(2):464-71. doi: 10.1006/bbrc.1999.1023.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Phosphorylation
  • Pyridines / pharmacology*
  • Serine / chemistry
  • Testicular Neoplasms / enzymology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / radiation effects
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Protein p53 / radiation effects*
  • Ultraviolet Rays
  • p38 Mitogen-Activated Protein Kinases


  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Tumor Suppressor Protein p53
  • Serine
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580