Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis

The activation of the transcription factor NF-kappa B often results in protection against apoptosis, In particular, proapoptotic tumor necrosis factor (TNF) signals are blocked hy proteins that are induced by NF-kappa B such as TNFR-associated factor 1 (TRAF1). Here se show that TRAF1 is cleaved after Asp-163 wen cells are induced to undergo apoptosis by Fas ligand (FasL). The C-terminal cleavage product blocks the induction of NF-kappa B by TNF and therefore functions as a dominant negative (DN) form of TRAF1. Our results suggest that the generation of DN-TRAF1 is part of a pro-apoptotic amplification system to assure rapid cell death. (C) 2000 Federation of European Biochemical Societies.