UVB-induced association of tumor necrosis factor (TNF) receptor 1/TNF receptor-associated factor-2 mediates activation of Rel proteins

AUTOR(ES)

Tobin, Derek

FONTE

The National Academy of Sciences

RESUMO

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-κB 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 TNFα 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.

Documentos Relacionados

• TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling.
• Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation
• Tumor necrosis factor (TNF)-mediated kinase cascades: Bifurcation of Nuclear Factor-κB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2
• Activation of Apoptosis Signal-Regulating Kinase 1 (ASK1) by Tumor Necrosis Factor Receptor-Associated Factor 2 Requires Prior Dissociation of the ASK1 Inhibitor Thioredoxin†
• CD30/TNF receptor-associated factor interaction: NF-kappa B activation and binding specificity.