Down-regulation of interferon gamma-activated STAT1 by UV light.
STAT1 is a cytoplasmic transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon-gamma (IFNgamma). Phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFNgamma-inducible genes. Here, we show that UV light interferes with tyrosine phosphorylation of STAT1, thereby hindering IFNgamma from exerting its biological effects. This effect is not due to a down-regulation of the IFNgamma receptor because phosphorylation of upstream-located Jak1 and Jak2 was not suppressed by UV light. In contrast, UV light had no effect on the phosphorylation of STAT3, which is activated by the proinflammatory cytokine interleukin 6. The UV light effect on STAT1 phosphorylation could be antagonized by vanadate, indicating at least partial involvement of a protein tyrosine phosphatase. Therefore, this study indicates a mechanism by which UV light can inhibit gene activation and suggests STAT1 as a new extranuclear UV target closely located to the membrane.
Aragane
Y
Y
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University Münster, Münster, Germany.
Kulms
D
D
Luger
T A
TA
Schwarz
T
T
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D015603:Keratinocytes; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000528:radiation effects; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis* / Q000528:radiation effects; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma; D015500:Chloramphenicol O-Acetyltransferase; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2