A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor.
Mutational analysis identified a C-terminal region of 78 amino acids within the cytoplasmic domain of the human 75 kDa tumor necrosis factor receptor (TNF-R2) that is required for signal transduction. This region was subsequently shown to mediate the interaction of cytoplasmic factors with TNF-R2. Two of these factors were isolated and molecularly cloned using biochemical purification and the yeast two-hybrid system. TNF receptor-associated factor 1 (TRAF1) and TRAF2 are the first two members of a novel protein family containing a novel C-terminal homology region, the TRAF domain. In addition, TRAF2 contains an N-terminal RING finger motif. TRAF1 and TRAF2 can form homo- and heterotypic dimers. Our analysis indicates that TRAF1 and TRAF2 are associated with the cytoplasmic domain of TNF-R2 in a heterodimeric complex in which TRAF2 contacts the receptor directly. TRAF1 interacts with TNF-R2 indirectly through heterodimer formation with TRAF2.
Rothe
M
M
Department of Molecular Biology, Genentech, Incorporated, South San Francisco, California 94080.
Wong
S C
SC
Henzel
W J
WJ
Goeddel
D V
DV
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2
D015703:Antigens, CD; D011506:Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2