title: Role of p38 mitogen-activated protein kinases in ultraviolet-B irradiation-induced activator protein 1 activation in human keratinocytes.
abstract: The effects of p38 mitogen-activated protein kinases on ultraviolet (UV) B irradiation-induced activator protein 1 (AP-1) activation were studied in a human keratinocyte cell line, HaCaT. The HaCaT cells were stably transfected with a plasmid containing a promoter fragment of human collagenase 1 driving a luciferase reporter gene. There is an AP-1-binding site within this fragment, without any other known transcription factor-binding sites. As we reported previously, UVB significantly induces activation of AP-1 and p38 in HaCaT cells. SB202190, a p38-specific inhibitor, inhibits UVB-induced p38 activation and c-fos gene expression. In the present study, we further examined the role of p38 in UVB-induced AP-1 activation. We observed that SB202190 strongly inhibited UVB-induced AP-1 transactivation at different time points and UVB doses in transfected HaCaT cells. Furthermore, SB202190 markedly inhibited UVB-induced AP-1 DNA binding as determined by mobility shift analyses. These results suggested, for the first time, that activation of p38 is required for UVB-induced AP-1 activation in human keratinocytes. In addition, a potential mechanism of UVB-induced AP-1 activation through p38 is to enhance AP-1 complex binding to its target DNA. Because c-fos gene expression plays a critical role in UVB-induced AP-1 activation and p38 is required for UVB-induced c-fos gene expression in HaCaT cells, as reported previously, a potential UVB signaling cascade for AP-1 activation in human keratinocytes has been determined. This cascade involves UVB, p38 activation, c-fos gene expression, and AP-1 activation.
authors.affiliation: Department of Radiation Oncology, Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: G T
authors.initials: GT
authors.lastname: Bowden
mesh_terms: D002460:Cell Line; D017364:Collagenases / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016762:Genes, fos / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D008156:Luciferases / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011725:Pyridines / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D009687:Nuclear Proteins; D011725:Pyridines; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D017364:Collagenases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole