A novel RING finger protein interacts with the cytoplasmic domain of CD40.
CD40 is a member of the tumor necrosis factor receptor family and, like other members, it appears to possess no intrinsic signaling capacity (e.g. kinase activity), suggesting that signal transduction is likely mediated by associating molecules. To identify such molecules, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the CD40 cytoplasmic domain. One such interacting protein, designated CD40-binding protein, has a N-terminal RING finger motif that is found in a number of DNA-binding proteins, including the V(D)J recombination activating gene RAG1. In addition, it contains a prominent central coiled-coil segment that may allow homo- or hetero-oligomerization. The C terminus possesses substantial homology to the tumor necrosis factor receptor-associated factor (TRAF) domain that is found in two proteins (TRAF1 and TRAF2) that associate with the cytoplasmic domain of the related 75-kDa tumor necrosis factor receptor. This is the first identification of a molecule that interacts with CD40 and whose sequence suggests a potential role in signaling.
Hu
H M
HM
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
O'Rourke
K
K
Boguski
M S
MS
Dixit
V M
VM
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D019013:CD40 Antigens; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C064658:RAG-1 protein