Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region

J Biol Chem. 1996 Nov 15;271(46):28745-8. doi: 10.1074/jbc.271.46.28745.


CD40 signalings play crucial roles in B-cell function. To identify molecules which transduce CD40 signalings, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer, designated TRAF6, has been molecularly cloned. TRAF6 has a tumor necrosis factor receptor (TNFR)-associated factor (TRAF) domain in its carboxyl terminus and has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain, which are also present in other TRAF family proteins. TRAF6 does not associate with the cytoplasmic tails of TNFR2, CD30, lymphotoxin-beta receptor, and LMP1 of Epstein-Barr virus. Deletion analysis showed that residues 246-269 of CD40 which are required for its association with TRAF2, TRAF3, and TRAF5 are dispensable for its interaction with TRAF6, whereas residues 230-245 were required. Overexpression of TRAF6 activates transcription factor NFkappaB, and its TRAF-C domain suppresses NFkappaB activation triggered by CD40 lacking residues 246-277. These results suggest that TRAF6 could mediate the CD40 signal that is transduced by the amino-terminal domain (230-245) of the CD40 cytoplasmic region and appears to be independent of other known TRAF family proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD40 Antigens / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • DNA, Complementary
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Protein Binding
  • Proteins*
  • Signal Transduction*
  • TNF Receptor-Associated Factor 6
  • Tumor Cells, Cultured


  • CD40 Antigens
  • Carrier Proteins
  • DNA, Complementary
  • NF-kappa B
  • Proteins
  • TNF Receptor-Associated Factor 6

Associated data

  • GENBANK/D84655