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Caspase‐induced inactivation of the anti‐apoptotic TRAF1 during Fas ligand‐mediated apoptosis
Author(s) -
Irmler Martin,
Steiner Véronique,
Ruegg Curzio,
Wajant Harald,
Tschopp Jürg
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01206-0
Subject(s) - apoptosis , fas ligand , tumor necrosis factor alpha , microbiology and biotechnology , programmed cell death , cleavage (geology) , death domain , caspase , chemistry , cancer research , transcription factor , caspase 8 , biology , immunology , biochemistry , gene , paleontology , fracture (geology)
The activation of the transcription factor NF‐κB often results in protection against apoptosis. In particular, pro‐apoptotic tumor necrosis factor (TNF) signals are blocked by proteins that are induced by NF‐κB such as TNFR‐associated factor 1 (TRAF1). Here we show that TRAF1 is cleaved after Asp‐163 when cells are induced to undergo apoptosis by Fas ligand (FasL). The C‐terminal cleavage product blocks the induction of NF‐κB 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.