UVB-induced association of tumor necrosis factor (TNF) receptor 1/TNF receptor-associated factor-2 mediates activation of Rel proteins.
Exposure of mammalian skin to UV light results in induced gene transcription, playing a role in inflammation, immunosuppression, and tumor promotion. One important group of transcription factors induced by UV radiation is composed of members of the Rel/NF-kappa B family, which are known to play a major role in the transcriptional activation of many genes encoding inflammatory cytokines, adhesion molecules, and viral proteins. However, the upstream events in the transduction of the UVB signal to Rel protein activity are, as yet, unknown. Here, we provide biochemical evidence that exposure of keratinocytes to UVB causes rapid association of tumor necrosis factor (TNF) receptor 1 with its downstream partner TRAF-2. The functional relevance of this association is demonstrated by experiments showing that expression of a dominant negative TNF receptor 1 or TRAF-2 protein inhibits UVB-induced Rel-dependent transcription. Inclusion of a neutralizing antibody toward TNF alpha has no effect on UVB activation of a Rel-responsive reporter gene. Therefore, UVB-induced activation of Rel proteins via TNF receptor 1, independent of ligand activation, is a key component in the UV response in keratinocytes.
Tobin
D
D
Department of Bioscience at Novum, Karolinska Institute, NOVUM, Huddinge, Sweden.
van Hogerlinden
M
M
Toftgård
R
R
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000528:radiation effects; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D047992:TNF Receptor-Associated Factor 2; D014466:Ultraviolet Rays
D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2