Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins.
The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of proteins interact with and transduce signals for members of the TNF receptor superfamily. TRAF1, TRAF2, and TRAF3 share a conserved C-terminal TRAF domain. TRAF2 plays a key role in transducing signals for activation of the transcription factor nuclear factor-kappaB (NF-kappaB). We have performed extensive mutational analysis on TRAF2, examining the requirements for NF-kappaB activation, self-association, and interaction with other molecules involved in TNF signaling. Examination of point mutants and TRAF2-TRAF3 chimeric proteins indicates that the N-terminal RING finger and two adjacent zinc fingers of TRAF2 are required for NF-kappaB activation. The two distinct TRAF-N and TRAF-C subdomains of the TRAF domain appear to independently mediate self-association and interaction with TRAF1. Interaction of TRAF2 with TNF-R2 and TRADD requires sequences at the C terminus of the TRAF-C domain, whereas interaction with the protein kinase receptor-interacting protein V(RIP) occurs via sequences at the N terminus of the TRAF-C domain. Thus, distinct domains of TRAF2 are involved in recruitment and signaling functions.
Takeuchi
M
M
Yamanouchi Pharmaceutical Co. Ltd., Tsukuba, Ibaraki 305, Japan.
Rothe
M
M
Goeddel
D V
DV
D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry; D006801:Humans; D046911:Macromolecular Substances; D016328:NF-kappa B / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000502:physiology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D015032:Zinc