Nakano H, Oshima H, Chung W, Williams-Abbott L, Ware C F, Yagita H, Okumura K
Department of Immunology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
J Biol Chem. 1996 Jun 21;271(25):14661-4. doi: 10.1074/jbc.271.25.14661.
Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal transducers for several members of the TNF receptor superfamily. We have identified a novel member of the TRAF family by degenerate oligonucleotide polymerase chain reaction amplification that contains a zinc RING finger and zinc finger motifs, a coiled-coil region, and a C-terminal "TRAF" homology domain. In vitro translated TRAF5 binds to the cytoplasmic region of the lymphotoxin-beta receptor (LT-betaR) but not to several other related receptors including CD40, both TNF receptors, Fas, and nerve growth factor receptor. TRAF5 and LT-betaR coimmunoprecipitate when overexpressed in COS7 cells. TRAF5 mRNA expression is found in all visceral organs and overlaps with LT-betaR. These features distinguish TRAF5 from the other members of the TRAF family. The transcription factor NF-kappaB is activated in HEK293 cells by overexpression of full-length TRAF5 but not a truncated form lacking the zinc binding region. Furthermore, overexpression of LT-betaR in HEK293 cells also results in activation of NF-kappaB, which is partially inhibited by the truncated TRAF5 mutant. These results show TRAF5 is functionally similar to TRAF2 in that both mediate activation NF-kappaB and implicate TRAF5 as a signal transducer for LT-betaR.
肿瘤坏死因子（TNF）受体相关因子（TRAFs）是TNF受体超家族中几个成员的信号转导分子。我们通过简并寡核苷酸聚合酶链反应扩增鉴定出TRAF家族的一个新成员，它包含一个锌指结构域、锌指基序、一个卷曲螺旋区域以及一个C端“TRAF”同源结构域。体外翻译的TRAF5能与淋巴毒素β受体（LT-βR）的胞质区域结合，但不与包括CD40、两种TNF受体、Fas和神经生长因子受体在内的其他几种相关受体结合。当在COS7细胞中过表达时，TRAF5和LT-βR能共同免疫沉淀。在所有内脏器官中均发现有TRAF5 mRNA表达，且与LT-βR的表达重叠。这些特征使TRAF5有别于TRAF家族的其他成员。在HEK293细胞中，全长TRAF5的过表达可激活转录因子NF-κB，而缺失锌结合区域的截短形式则不能。此外，在HEK293细胞中过表达LT-βR也会导致NF-κB的激活，而截短的TRAF5突变体可部分抑制这种激活。这些结果表明，TRAF5在功能上与TRAF2相似，二者均介导NF-κB的激活，提示TRAF5是LT-βR的信号转导分子。
