A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40.
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.
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La Jolla Cancer Research Foundation, Oncogene & Tumor Suppressor Gene Program, CA 92037.
Irie
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Reed
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D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001483:Base Sequence; D019013:CD40 Antigens; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D002352:Carrier Proteins; D018076:DNA, Complementary; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins