Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) were identi fied as signal transducers for the TNF receptor superfamily. However, the e xact roles of TRAF2 and TRAF5 in TNF-induced NF-kappaB activation still rem ain controversial. To address this issue, we generated TRAF2 and TRAF5 doub le knockout (DKO) mice. TNF- but not interleukin-1-induced nuclear transloc ation of NF-kappaB was severely impaired in murine embryonic fibroblasts (M EFs) derived from DKO mice. Moreover, DKO MEFs were more susceptible to TNF -induced cytotoxicity than TRAF2 knockout MEFs. Collectively, these results indicate that both TRAF2 and TRAF5 are involved in TNF-induced NF-kappaB a ctivation and protection from cell death.