Wajant H, Mühlenbeck F, Scheurich P
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
J Mol Evol. 1998 Dec;47(6):656-62. doi: 10.1007/pl00006423.
Many members of the tumor necrosis factor (TNF) receptor superfamily and the interleukin-1 (IL-1) receptor engage intracellular signaling pathways including the nuclear factor kappaB (NF-kappaB)-, c-jun N-terminal kinase (JNK)-, and extracellular signal-regulated kinase (ERK) pathways by direct or indirect interaction with TNF receptor-associated factor (TRAF) molecules. To date, six mammalian members of the TRAF family have been identified. Searching public databases with a sequence pattern comprising 19 conserved amino acid residues derived from the carboxyl-terminal part of the TRAF homology domain, we found significant sequence homologies to a stretch of genomic DNA from Caenorhabditis elegans which encodes 1 of 12 exons of a putative protein. The sequence of this putative protein shows up to 29% sequence identity to the mammalian TRAFs and is therefore designated C. elegans TRAF (CeTRAF). The CeTRAF molecule has an amino-terminal RING finger motif followed by four zinc finger structures and a carboxyl-terminal TRAF domain, a composition which is also found in most of the mammalian TRAFs. Reverse transcription-PCR and sequencing analysis of the respective amplicon clearly demonstrates that CeTRAF is in fact transcribed in C. elegans. The existence of a member of the TRAF family in C. elegans provides strong evidence for evolutionary conserved pathways linking cell surface receptors to activation of JNK, ERK, and NF-kappaB.
肿瘤坏死因子(TNF)受体超家族和白细胞介素-1(IL-1)受体的许多成员通过与TNF受体相关因子(TRAF)分子直接或间接相互作用,参与细胞内信号传导途径,包括核因子κB(NF-κB)、c-jun氨基末端激酶(JNK)和细胞外信号调节激酶(ERK)途径。迄今为止,已鉴定出TRAF家族的六个哺乳动物成员。用包含来自TRAF同源结构域羧基末端部分的19个保守氨基酸残基的序列模式搜索公共数据库,我们发现与秀丽隐杆线虫一段基因组DNA有显著的序列同源性,该基因组DNA编码一种假定蛋白质的12个外显子中的1个。这种假定蛋白质的序列与哺乳动物TRAF的序列同一性高达29%,因此被命名为秀丽隐杆线虫TRAF(CeTRAF)。CeTRAF分子具有一个氨基末端的RING指基序,后面跟着四个锌指结构和一个羧基末端的TRAF结构域,这种组成在大多数哺乳动物TRAF中也能找到。对相应扩增子的逆转录PCR和测序分析清楚地表明CeTRAF实际上在秀丽隐杆线虫中被转录。秀丽隐杆线虫中存在TRAF家族成员,为将细胞表面受体与JNK、ERK和NF-κB激活联系起来的进化保守途径提供了有力证据。