Anatomy of TRAF2 - Distinct domains for nuclear factor-kappa B activation and association with tumor necrosis factor signaling proteins

被引:281
作者
Takeuchi, M
Rothe, M
Goeddel, DV
机构
[1] TULARIK INC, San Francisco, CA 94080 USA
[2] YAMANOUCHI PHARMACEUT CO LTD, TSUKUBA, IBARAKI 305, JAPAN
关键词
D O I
10.1074/jbc.271.33.19935
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-kappa B (NF-kappa B). We have performed extensive mutational analysis on TRAF2, examining the requirements for NF-kappa B 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-kappa B 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.
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页码:19935 / 19942
页数:8
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