The F-box protein Fbxo7 interacts with human inhibitor of apoptosis protein cIAP1 and promotes cIAP1 ubiquitination
The F-box protein Fbxo7 interacts with human inhibitor of apoptosis protein cIAP1 and promotes cIAP1 ubiquitination
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DOI：
10.1016/j.bbrc.2006.02.061
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发表时间：
2006-04-21
影响因子：
3.1
通讯作者：
Yuo, CY
中科院分区：
文献类型：
--
作者：
Chang, YF;Cheng, CM;Yuo, CY
人cIAP1蛋白是细胞凋亡抑制蛋白(IAPs)的一员，参与细胞凋亡调控和细胞周期及细胞内信号转导等多种功能。为了寻找与CIAP调控相关的新蛋白，我们进行了酵母双杂交筛选，并将F-box蛋白Fbxo7鉴定为CIAP1相互作用蛋白。免疫共沉淀实验表明，CIAP1在人细胞内能与Fbxo7相互作用。当cIAP1和Fbxo7在细胞中共表达时，cIAP1和Fbxo7显著地共定位于细胞质和细胞核中，其中相当多的共同定位于靠近细胞核的一个或几个不同的高尔基样结构。更重要的是。我们发现Fbxo7的过表达促进了cIAP1的泛素化。由于F-box蛋白是SCF泛素蛋白连接酶的特异性决定亚基，我们的结果表明，Fbxo7可以介导SCF泛素蛋白连接酶对cIAP1的泛素化，从而在cIAP1功能的调控中具有重要意义。(C)2006 Elsevier Inc.保留所有权利。
Human cIAP1 protein is a member of the inhibitor of apoptosis proteins (IAPs) that are involved in apoptosis regulation and an increasing number of other functions, including cell cycle and intracellular signal transduction. In order to identify novel proteins involved in cIAP regulation, we performed a yeast two-hybrid screen and identified an F-box protein Fbxo7 as a cIAP1 interacting protein. Co-immunoprecipitation assay showed that cIAP1 can interact with Fbxo7 in human cells. When co-expressed in cells, cIAP1 and Fbxo7 co-localized remarkably both in the cytoplasm and nucleus, and considerable amounts of these often co-localized at one or few distinct Golgi-like structures close to the nucleus. Furthermore. we showed that overexpression of Fbxo7 promotes the ubiquitination of cIAP1. Since F-box proteins are specificity determining subunits of SCF ubiquitin protein ligases, our results suggest that Fbxo7 can mediate the ubiquitination of cIAP1 by SCF ubiquitin protein ligase and thus have important implication in the regulation of cIAP1 function. (c) 2006 Elsevier Inc. All rights reserved.