A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains
A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains
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DOI：
10.1074/jbc.m100354200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Reed, JC
中科院分区：
文献类型：
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作者：
Zapata, JM;Pawlowski, K;Reed, JC
我们利用生物信息学方法在人类中鉴定了三种新的含有肿瘤坏死因子受体相关因子(TRAF)结构域的蛋白质，包括：MUL，多丝分裂综合征致病基因的产物；USP7(Hausp)，一种泛素蛋白酶；以及SPOP，一种含有POZ结构域的蛋白。与经典的参与肿瘤坏死因子受体(TNFR)信号转导的TRAF家族蛋白不同，MUL、USP7和SPOP的TRAF结构域(TD)位于这些蛋白的NR、末端或中心区附近，而不是位于羧基末端。MUL和USP7在体外能通过其TDS与所有已知的TRAF家族蛋白(TRAF1、TRAF2、TRAF3、TRAF4、TRAF5和TRAF6)结合，而SPOP的TD只与TRAF1和TRAF6弱相互作用。MUL的TD也与自身相互作用，而USP7：和SPOP的TD不是自结合的。瞬时转基因分析表明，这些蛋白的TD对于抑制TRAF2和TRAF6以及某些TRAF结合的肿瘤坏死因子家族受体诱导的NF-kappaB的诱导是必要的和充分的。相反，SPOP末端并不抑制核因子-kappaB的诱导。免疫荧光共聚焦显微镜显示MUL定位于胞浆小体，靶向这些结构是由MUL蛋白中的RBCC三段结构域介导的。USP7以TD依赖的方式主要定位于细胞核。数据库搜索显示，在酵母、原生生物、植物、无脊椎动物和哺乳动物等真核生物中，含有与MUL、USP7和SPOP中发现的TDS同源的多个蛋白质，表明TD家族的这个分支来自一个古老的基因。我们提出了这个蛋白质大家族的绰号TEF(TD-包容因子)。
We have identified three new tumor necrosis factor-receptor associated factor (TRAF) domain-containing proteins in humans using bioinformatics approaches, including: MUL, the product of the causative gene in Mulibrey Nanism syndrome; USP7 (HAUSP), an ubiquitin protease; and SPOP, a POZ domain-containing protein. Unlike classical TRAF family proteins involved in TNF family receptor (TNFR) signaling, the TRAF domains (TDs) of MUL, USP7, and SPOP are located near the NR, termini or central region of these proteins, rather than carboxyl end. MUL and USP7 are capable of binding in vitro via their TDs to all of the previously identified TRAF family proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, and TRAF6), whereas the TD of SPOP interacts weakly with TRAF1 and TRAF6 only. The TD of MUL also interacted with itself, whereas the TDs of USP7: and SPOP did not self-associate, Analysis of various MUL and USP7 mutants by transient transfection assays indicated that the TDs of these proteins are necessary and sufficient for suppressing NF-kappaB induction by TRAF2 and TRAF6 as well as certain TRAF-binding TNF family receptors. In contrast, the TIP of SPOP did not inhibit NF-kappaB induction. Immunofluorescence confocal microscopy indicated that MUL localizes to cytosolic bodies, with targeting to these structures mediated by a RBCC tripartite domain within the MUL protein. USP7 localized predominantly to the nucleus, in a TD-dependent manner. Data base searches revealed multiple proteins containing TDs homologous to those found in MUL, USP7, and SPOP throughout eukaryotes, including yeast, protists, plants, invertebrates, and mammals, suggesting that this branch of the TD family arose from an ancient gene. We propose the moniker TEFs (TD-encompassing factors) for this large family of proteins.