Abstract
Tumor necrosis factor receptor type 1 (TNF-R1) contains a cytoplasmic death domain that is required for the signaling of TNF activities such as apoptosis and nuclear factor kappa B (NF-kappaB) activation. Normally, these signals are generated only after TNF-induced receptor aggregation. However, TNF-R1 self-associates and signals independently of ligand when overexpressed. This apparent paradox may be explained by silencer of death domains (SODD), a widely expressed approximately 60-kilodalton protein that was found to be associated with the death domain of TNF-R1. TNF treatment released SODD from TNF-R1, permitting the recruitment of proteins such as TRADD and TRAF2 to the active TNF-R1 signaling complex. SODD also interacted with death receptor-3 (DR3), another member of the TNF receptor superfamily. Thus, SODD association may be representative of a general mechanism for preventing spontaneous signaling by death domain-containing receptors.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Apoptosis
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Fas-Associated Death Domain Protein
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Humans
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Jurkat Cells
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Molecular Sequence Data
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Mutation
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NF-kappa B / metabolism
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Protein Binding
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Proteins / metabolism
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Receptor Aggregation
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Receptor-Interacting Protein Serine-Threonine Kinases
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Receptors, Tumor Necrosis Factor / chemistry
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Member 25
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
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U937 Cells
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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BAG4 protein, human
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Carrier Proteins
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FADD protein, human
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Fas-Associated Death Domain Protein
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NF-kappa B
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Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 25
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins
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TNF Receptor-Associated Factor 1
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TNF Receptor-Associated Factor 2
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TNFRSF25 protein, human
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Tumor Necrosis Factor-alpha
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RIPK1 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinases