Anatomy of TRAF2. Distinct Domains for Nuclear factor-kappaB Activation and Association With Tumor Necrosis Factor Signaling Proteins

J Biol Chem. 1996 Aug 16;271(33):19935-42. doi: 10.1074/jbc.271.33.19935.

Abstract

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of proteins interact with and transduce signals for members of the TNF receptor superfamily. TRAF1, TRAF2, and TRAF3 share a conserved C-terminal TRAF domain. TRAF2 plays a key role in transducing signals for activation of the transcription factor nuclear factor-kappaB (NF-kappaB). We have performed extensive mutational analysis on TRAF2, examining the requirements for NF-kappaB activation, self-association, and interaction with other molecules involved in TNF signaling. Examination of point mutants and TRAF2-TRAF3 chimeric proteins indicates that the N-terminal RING finger and two adjacent zinc fingers of TRAF2 are required for NF-kappaB activation. The two distinct TRAF-N and TRAF-C subdomains of the TRAF domain appear to independently mediate self-association and interaction with TRAF1. Interaction of TRAF2 with TNF-R2 and TRADD requires sequences at the C terminus of the TRAF-C domain, whereas interaction with the protein kinase receptor-interacting protein V(RIP) occurs via sequences at the N terminus of the TRAF-C domain. Thus, distinct domains of TRAF2 are involved in recruitment and signaling functions.

MeSH terms

  • Antigens, CD / chemistry
  • Binding Sites
  • DNA Mutational Analysis
  • DNA-Binding Proteins / chemistry
  • Humans
  • Macromolecular Substances
  • NF-kappa B / chemistry*
  • Protein Binding
  • Proteins / chemistry*
  • Proteins / physiology
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type II
  • Signal Transduction
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha / physiology*
  • Zinc / chemistry
  • Zinc Fingers

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • Macromolecular Substances
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Zinc