A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40

• Published in: FEBS letters 1995-01, Vol.358 (2), p.113-118
• Main Authors: Sato, Takaaki, Irie, Shinji, Reed, John C.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - metabolism; Base Sequence; Carrier Proteins - metabolism; CD40; CD40 Antigens; Cells, Cultured; Cloning, Molecular; Cytosol - metabolism; DNA, Complementary; Humans; Molecular Sequence Data; Open Reading Frames; Protein Binding; Sequence Homology, Amino Acid; Signal Transduction; TNF Receptor-Associated Factor 3; TRAF; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)01406-Q

CD40 is a member of the tumor necrosis factor receptor (TNF-R) family that regulates B-lymphocyte proliferation, immunoglobulin class-switching, and apoptosis through poorly defined signal transduction mechanisms. Using a yeast two-hybrid method, cDNAs were obtained that encode a novel protein, CD40-associated protein-1 (CAP-1), which binds specifically to the cytosolic domain of CD40 but not TNF-R1, TNF-R2, or Fas. The CAP-1 protein contains a C-terminal domain that shares strong amino acid sequence homology with a unique domain found recently in two putative signal transducing proteins that bind to the TNF-R2 cytosolic tail, TRAF1 and TRAF2. This C-terminal region of CAP-1 was sufficient to mediate binding to CD40 and homodimerization of CAP-1 proteins. The N-terminal portion of CAP-1 contains a RING finger motif and three zinc finger-like domains similar to those found in several regulatory proteins that interact with DNA or RNA. CAP-1 thus represents a new member of a family of potential signal transducing proteins that contain a conserved domain (the TRAF domain), bind to the cytosolic regions of particular members of TNF-R family proteins, and that can form homo- and heterotypic dimers.