Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region
Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region
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DOI：
10.1074/jbc.271.46.28745
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发表时间：
1996-11-15
影响因子：
4.8
通讯作者：
Inoue, J
中科院分区：
文献类型：
--
作者：
Ishida, T;Mizushima, S;Inoue, J
CD 40信号传导在B细胞功能中起着至关重要的作用。为了鉴定阻断CD 40信号传导的分子，我们利用酵母双杂交系统克隆了编码结合CD 40胞质尾区的蛋白质的cDNA。编码一个假定的信号转导，指定TRAF 6的cDNA已被分子克隆。TRAF 6在其羧基末端具有肿瘤坏死因子受体（TNFR）相关因子（TRAF）结构域，并且具有RING指结构域、锌指簇和卷曲螺旋结构域，这些结构域也存在于其他TRAF家族蛋白中。TRAF 6不与TNFR 2、CD 30、Epstein-Barr病毒的LPS-β受体和LMP 1的胞质尾区相关。缺失分析显示，CD 40的残基246-269（其与TRAF 2、TRAF 3和TRAF 5结合所需）对于其与TRAF 6的相互作用是缺失的，而残基230-245是必需的。TRAF 6的过表达激活转录因子NF κ B B，并且其TRAF-C结构域抑制由缺少残基246-277的CD 40触发的NF κ B激活。这些结果表明TRAF 6可以介导由CD 40胞质区的氨基末端结构域（230-245）转导的CD 40信号，并且似乎独立于其他已知的TRAF家族蛋白。
CD40 signalings play crucial roles in B-cell function. To identify molecules which transduce CD40 signalings, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer, designated TRAF6, has been molecularly cloned. TRAF6 has a tumor necrosis factor receptor (TNFR)-associated factor (TRAF) domain in its carboxyl terminus and has a RING finger domain, a cluster of zinc fingers and a coiled coil domain, which are also present in other TRAF family proteins. TRAF6 does not associate with the cytoplasmic tails of TNFR2, CD30, lymphotoxin-beta receptor, and LMP1 of Epstein-Barr virus. Deletion analysis showed that residues 246-269 of CD40 which are required for its association with TRAF2, TRAF3, and TRAF5 are dispensable for its interaction with TRAF6, whereas residues 230-245 were required. Overexpression of TRAF6 activates transcription factor NF kappa B, and its TRAF-C domain suppresses NF kappa B activation triggered by CD40 lacking residues 246-277. These results suggest that TRAF6 could mediate the CD40 signal that is transduced by the amino-terminal domain (230-245) of the CD40 cytoplasmic region and appears to be independent of other known TRAF family proteins.