UV-A-induced AP-1 activation requires the Raf/ERK pathway in human NCTC 2544 keratinocytes.
UV-A irradiation causes a dose-dependent activation of ERK in human NCTC 2544 keratinocytes. The specific inhibition of either ERK activity or Raf kinase activity impedes the activation of AP-1 DNA binding induced by UV-A. In addition, UV-A raises AP-1 promoter transcriptional activity, which is downregulated in NCTC 2544 cells expressing an inactive mutant of Raf-1. We found that singlet oxygen might be one of the mediators in both UV-A-induced AP-1 DNA binding and transcriptional activity. These results strongly suggest that UV-A-induced AP-1 activity requires the Raf-ERK pathway and imply a singlet oxygen effector.
Djavaheri-Mergny
M
M
Institut de Recherche sur la peau, Inserm 523, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75475 Paris, France. Mojgan.Mergny@curie.fr
Dubertret
L
L
D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010100:Oxygen / Q000737:chemistry / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D018808:Transcription Factor AP-1; D004247:DNA; D019908:Proto-Oncogene Proteins c-raf; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen