Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14053-8. doi: 10.1073/pnas.93.24.14053.


CD30 is a member of the tumor necrosis factor receptor superfamily, which can transduce signals for proliferation, death, or nuclear factor kappa B (NF-kappa B) activation. Investigation of CD30 signaling pathways using a yeast two-hybrid interaction system trapped a cDNA encoding the tumor necrosis factor receptor-associated factor (TRAF)-2 TRAF homology domain. TRAF-1 and TRAF-3 also interacted with CD30, and > 90% of in vitro-translated TRAF-1 or -2, or 50% of TRAF-3, bound to the CD30 cytoplasmic domain. TRAF-1, -2, and -3 bound mostly, but not exclusively, to the carboxyl-terminal 36 residues of CD30. The binding was strongly inhibited by a CD30 oligopeptide centered around a PXQXT (where X is any amino acid) motif shared with CD40 and the Epstein-Barr virus transforming protein LMP1, indicating that this motif in CD30 is an important determinant of TRAF-1, -2 or -3 interaction. At least 15% of TRAF-1, -2, or -3 associated with CD30 when coexpressed in 293 cells. The association was not affected by CD30 cross-linking. However, cross-linking of CD30 activated NF-kappa B. NF-kappa B activation was dependent on the carboxyl-terminal 36 amino acids of CD30 that mediate TRAF association. TRAF-2 has been previously shown to have a unique role in TRAF-mediated NF-kappa B activation, and NF-kappa B activation following CD30 cross-linking was blocked by a dominant negative TRAF-2 mutant. These data indicate that CD30 cross-linking-induced NF-kappa B activation is predominantly TRAF-2-mediated.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cytoplasm / metabolism
  • Humans
  • Ki-1 Antigen / biosynthesis
  • Ki-1 Antigen / chemistry
  • Ki-1 Antigen / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Proteins / chemistry
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3
  • Transcriptional Activation
  • Transfection


  • Ki-1 Antigen
  • NF-kappa B
  • Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 3