RETRACTED: 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

Abstract

CD30 is a member of the tumor necrosis factor receptor superfamily, which can transduce signals for proliferation, death, or nuclear factor kappa B (NF-κB) 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-κB. NF-κB 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-κB activation, and NF-κB activation following CD30 cross-linking was blocked by a dominant negative TRAF-2 mutant. These data indicate that CD30 cross-linking-induced NF-κB activation is predominantly TRAF-2-mediated.

Lymphotoxin-β receptor signaling complex: Role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor κB

“…TRAF3 was originally described as a CD40-binding protein and as a protein associated with LMP1, a dominant oncogene product of Epstein-Barr virus (31)(32)(33)(34). TRAF3 also interacts with the cytoplasmic regions of LT␤R, TNFR80, and CD30, but not significantly with TNFR60 or Fas (34)(35)(36). Like most other TRAFs, TRAF3 has an N-terminal RING finger and several zinc finger domains, a coiled-coil region, and a C-terminal receptor-binding domain that is homologous to other TRAFs (37).…”

“…Like most other TRAFs, TRAF3 has an N-terminal RING finger and several zinc finger domains, a coiled-coil region, and a C-terminal receptor-binding domain that is homologous to other TRAFs (37). Other members of the TRAF family interact with LT␤R, TNFR80, CD40, and CD30 (34)(35)(36)(37)(38)(39)(40). Overexpression of TRAF2 or TRAF5 can activate NF-B, a transcription factor controlling expression of genes involved in immune and inflammatory responses (41,42).…”

Increased Expression and Activation of CD30 Induce Apoptosis in Human Blood Eosinophils

“…The full-length CD30 molecule is a 120-kDa heavily glycosylated protein. The extracellular portion of CD30 can be proteolytically cleaved by zinc-metalloprotease to produce an 85/90 kDa soluble form (27)(28)(29). CD30 activation participates in a variety of biological effects depending on cell type, ranging from cell proliferation and activation to apoptosis (20 -32).…”

A Novel Role of CD30/CD30 Ligand Signaling in the Generation of Long-Lived Memory CD8+ T Cells

“…CD30 uses TRAF molecules, particularly TRAF2 and TRAF5, to induce downstream signals (55)(56)(57). TRAF2 is thought to be responsible for NF-B activation and for the antiapoptotic effect mediated by CD30 (55)(56)(57). Although lymphocyte homeostasis does not seem to be affected in TRAF5 Ϫ/Ϫ mice, TRAF2…”

“…It is also possible that CD30 signaling provides direct survival signal or the responsiveness to memory CD8 ϩ T cells in addition to up-regulation of the expression of homing receptors. CD30 uses TRAF molecules, particularly TRAF2 and TRAF5, to induce downstream signals (55)(56)(57). TRAF2 is thought to be responsible for NF-B activation and for the antiapoptotic effect mediated by CD30 (55)(56)(57).…”