TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling
TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling
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DOI：
10.1073/pnas.93.18.9437
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发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Inoue, J
中科院分区：
文献类型：
--
作者：
Ishida, T;Tojo, T;Inoue, J
从CD 40发出的信号在B细胞功能中起着至关重要的作用。为了鉴定抑制CD 40信号传导的分子，我们使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蛋白，指定TRAF 5的cDNA已被分子克隆。TRAF 5在其羧基末端具有肿瘤坏死因子受体相关因子（TRAF）结构域，并且与TRAF 3（也称为CRAF 1、CD 40 bp或CD 40 -1，一种先前鉴定的CD 40相关因子）最同源。氨基末端具有RING指结构域、锌指簇和卷曲螺旋结构域，其也存在于TRAF家族蛋白的除TRAF 1以外的其他成员中。体外结合试验显示TRAF 5与CD 40的胞质尾区相关，但不与TRAF 2相关的肿瘤受体因子受体2型的胞质尾区相关。基于TRAF 5和各种CD 40突变体之间的关联的分析，CD 40的残基230-269是与TRAF 5关联所必需的。与TRAF 3相反，TRAF 5的过表达激活转录因子核因子κ B。此外，氨基末端截短形式的TRAF 5抑制CD 40介导的CD 23表达诱导，如TRAF 3的情况。这些结果表明，TRAF 5和TRAF 3可能参与CD 40发出的共同和不同的信号通路。
Signals emanating from CD40 play crucial roles in B-cell function, To identify molecules that transduce CD40 signalings, we have used the yeast two-hybrid system to clone cDNAs encoding proteins that bind the cytoplasmic tail of CD40. A cDNA encoding a putative signal transducer protein, designated TRAF5, has been molecularly cloned. TRAF5 has a tumor necrosis factor receptor-associated factor (TRAF) domain in its carboxyl terminus and is most homologous to TRAF3, also known as CRAF1, CD40bp, or LAP-1, a previously identified CD40-associated factor. The amino terminus has a RING finger domain, a cluster of zinc fingers and a coiled-coil domain, which are also present in other members of the TRAF family protein except for TRAF1. In vitro binding assays revealed that TRAF5 associates with the cytoplasmic tail of CD40, but not with the cytoplasmic tail of tumor receptor factor receptor type 2, which associates with TRAF2. Based on analysis of the association between TRAF5 and various CD40 mutants, residues 230-269 of CD40 are required for the association with TRAF5. In contrast to TRAF3, overexpression of TRAF5 activates transcription factor nuclear factor kappa B. Furthermore, amino-terminally truncated forms of TRAF5 suppress the CD40-mediated induction of CD23 expression, as is the case with TRAF3. These results suggest that TRAF5 and TRAF3 could be involved in both common and distinct signaling pathways emanating from CD40.