TRUSS, a tumor necrosis factor receptor-1-interacting protein, activates c-Jun NH(2)-terminal kinase and transcription factor AP-1.

Tumor necrosis factor-alpha (TNF-alpha) induces the transcriptional activation of numerous genes involved in the inflammatory response. The recently identified protein TRUSS was investigated for its role in TNF-alpha-induced activation of c-Jun-NH(2) terminal kinase (JNK) and transcription factor, AP-1. Ectopic expression of TRUSS activated JNK and AP-1 in the absence and presence of TNF-alpha stimulation. The C-terminal region of TRUSS interacted with TNF receptor-associated factor-2 (TRAF2) and co-expression of dominant-inhibitory TRAF2 with TRUSS inhibited AP-1 activation, suggesting that TRUSS signaling occurs upstream of TRAF2. Further, a dominant-inhibitory mutant of TRUSS inhibited TNF-alpha-induced AP-1 activation. These findings suggest that TRUSS activates JNK in a TRAF2-dependent fashion and is involved in TNF-alpha-induced AP-1 activation via JNK kinases.