Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis.
The activation of the transcription factor NF-kappaB often results in protection against apoptosis. In particular, pro-apoptotic tumor necrosis factor (TNF) signals are blocked by proteins that are induced by NF-kappaB 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-kappaB 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.
Irmler
M
M
Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066, Epalinges, Switzerland.
Steiner
V
V
Ruegg
C
C
Wajant
H
H
Tschopp
J
J
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002051:Burkitt Lymphoma; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D053222:Fas Ligand Protein; D005354:Fibrosarcoma; D006801:Humans; D007668:Kidney; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010446:Peptide Fragments; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D047990:TNF Receptor-Associated Factor 1; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020169:Caspases