TRAF1 is a TNF inducible regulator of NF-kappaB activation

Abstract

Tumor necrosis factor receptor (TNFR)-associated factor TRAF1 was first identified as a component of the TNFR2 signalling complex. Unlike the other members of the TRAF family, TRAF1 lacks the N-terminal ring finger motif and has a tissue specific expression. Here we demonstrate that expression of TRAF1 is induced by TNF and the protein kinase C (PKC) activator PMA, but not by interleukin-1 (IL-1). TNF-induced upregulation of TRAF1 could be prevented by pretreatment of the cells with the proteasome inhibitor MG-132, whereas the PKC inhibitor Ro31-8220 was without effect. Interestingly, overexpression of TRAF1 in HEK293T completely prevented NF-kappaB activation induced by TNF, IL-1, or overexpression of TRAF2 or TRAF6. These data suggest that inducible expression of TRAF1 may serve a negative regulatory function in NF-kappaB signalling pathways.