TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways

Cell. 1996 Jan 26;84(2):299-308. doi: 10.1016/s0092-8674(00)80984-8.

Abstract

Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways. Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Antigens, CD / metabolism
  • Antigens, CD / physiology*
  • Apoptosis / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Fas-Associated Death Domain Protein
  • Humans
  • Interleukin-1 / pharmacology
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / physiology
  • Proteins*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type I
  • Sequence Deletion
  • Signal Transduction / physiology*
  • TNF Receptor-Associated Death Domain Protein
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Transcriptional Activation
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Carrier Proteins
  • FADD protein, human
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
  • Interleukin-1
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • TNF Receptor-Associated Death Domain Protein
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tradd protein, mouse
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Tumor Necrosis Factor-alpha

Associated data

  • GENBANK/U43184