Prevention of constitutive TNF receptor 1 signaling by silencer of death domains

Science. 1999 Jan 22;283(5401):543-6. doi: 10.1126/science.283.5401.543.

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

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Apoptosis
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Fas-Associated Death Domain Protein
  • Humans
  • Jurkat Cells
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / metabolism
  • Protein Binding
  • Proteins / metabolism
  • Receptor Aggregation
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • BAG4 protein, human
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 25
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Fusion Proteins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNFRSF25 protein, human
  • Tumor Necrosis Factor-alpha
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases

Associated data

  • GENBANK/AF111116