Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins
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Burkitt Lymphoma
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Caspases / metabolism*
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Cell Line
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Fas Ligand Protein
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Fibrosarcoma
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Humans
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Kidney
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Membrane Glycoproteins / pharmacology
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Membrane Glycoproteins / physiology*
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NF-kappa B / metabolism
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Peptide Fragments / pharmacology
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Proteins / antagonists & inhibitors
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Proteins / genetics
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Proteins / physiology*
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Receptors, Tumor Necrosis Factor / physiology
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Signal Transduction
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TNF Receptor-Associated Factor 1
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TNF-Related Apoptosis-Inducing Ligand
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology
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fas Receptor / physiology*
Substances
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Apoptosis Regulatory Proteins
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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NF-kappa B
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Peptide Fragments
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Proteins
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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TNF Receptor-Associated Factor 1
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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fas Receptor
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Caspases