UVB-INDUCED ASSOCIATION OF TUMOR-NECROSIS-FACTOR (TNF) RECEPTOR-1 TNFRECEPTOR-ASSOCIATED FACTOR-II MEDIATES ACTIVATION OF REL PROTEINS

Exposure of mammalian skin to UV light results in induced gene transcr iption, playing a role in inflammation, immunosuppression, and tumor p romotion. One important group of transcription factors induced by UV r adiation is composed of members of the Rel/NF-kappa B family, which ar e 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 rapi d association of tumor necrosis factor (TNF) receptor 1 with its downs tream partner TRAF-2. The functional relevance of this association is demonstrated by experiments showing that expression of a dominant nega tive TNF receptor 1 or TRAF-2 protein inhibits UVB-induced Rel-depende nt transcription. Inclusion of a neutralizing antibody toward TNF alph a has no effect on UVB activation of a Rel-responsive reporter gene. T herefore, UVB-induced activation of Rel proteins via TNF receptor 1, i ndependent of ligand activation, is a key component in the UV response in keratinocytes.