CIF-1, a shared subunit of the COP9/signalosome and eukaryotic initiation factor 3 complexes, regulates MEL-26 levels in the Caenorhabditis elegans embryo
CIF-1, a shared subunit of the COP9/signalosome and eukaryotic initiation factor 3 complexes, regulates MEL-26 levels in the Caenorhabditis elegans embryo
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DOI：
10.1128/mcb.01724-06
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Pintard, Lionel
中科院分区：
文献类型：
--
作者：
Luke-Glaser, Sarah;Roy, Marcia;Pintard, Lionel
COP 9/信号体（CSN）是一种进化上保守的大分子复合物，其主要通过从cullin亚基去除泛素样蛋白Nedd 8来调节cullin-RING连接酶（CRL）类E3泛素连接酶。在秀丽隐杆线虫胚胎中，CSN通过CUL-3去螺旋化控制微管切割蛋白MEI-1的降解。然而，CSN功能的分子机制及其亚基组成仍有待阐明。在这里，使用蛋白质组学的方法，我们已经确定了CSN和CUL-3复合物从C。线虫胚胎我们表明，CSN的物理相互作用与CUL-3为基础的CRL和调节其活动，通过抵消自催化不稳定的底物特异性适配器MEL-26。重要的是，我们确定了未表征的蛋白K08F11.3/CIF-1（CSN-真核起始因子3 [eIF 3]）作为CSN复合物的化学计量和功能上重要的亚基。CIF-1似乎是C. elegans基因组，但它也表现出广泛的序列相似性eIF 3 m家族成员，这是蛋白质翻译的起始所需的。实际上，CIF-1结合eIF-3.F，并且CIF-1的失活损害体内翻译。总之，我们的研究结果表明，CIF-1是CSN和eIF 3复合物的共享亚基，因此可能连接蛋白质翻译和降解。
The COP9/signalosome (CSN) is an evolutionarily conserved macromolecular complex that regulates the cullin-RING ligase (CRL) class of E3 ubiquitin ligases, primarily by removing the ubiquitin-like protein Nedd8 from the cullin subunit. In the Caenorhabditis elegans embryo, the CSN controls the degradation of the microtubule-severing protein MEI-1 through CUL-3 deneddylation. However, the molecular mechanisms of CSN function and its subunit composition remain to be elucidated. Here, using a proteomic approach, we have characterized the CSN and CUL-3 complexes from C. elegans embryos. We show that the CSN physically interacts with the CUL-3-based CRL and regulates its activity by counteracting the autocatalytic instability of the substrate-specific adaptor MEL-26. Importantly, we identified the uncharacterized protein K08F11.3/CIF-1 (for CSN-eukaryotic initiation factor 3 [eIF3]) as a stoichiometric and functionally important subunit of the CSN complex. CIF-1 appears to be the only ortholog of Csn7 encoded by the C. elegans genome, but it also exhibits extensive sequence similarity to eIF3m family members, which are required for the initiation of protein translation. Indeed, CIF-1 binds eIF-3.F and inactivation of cif-1 impairs translation in vivo. Taken together, our results indicate that CIF-1 is a shared subunit of the CSN and eIF3 complexes and may therefore link protein translation and degradation.