The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.
The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.
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去泛素化酶复合物 BRISC 是哺乳动物细胞中正确有丝分裂纺锤体组装所必需的。
DOI：
10.1083/jcb.201503039
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发表时间：
2015-07-20
期刊：
影响因子：
--
通讯作者：
Shao G
中科院分区：
文献类型：
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作者：
Yan K;Li L;Wang X;Hong R;Zhang Y;Yang H;Lin M;Zhang S;He Q;Zheng D;Tang J;Yin Y;Shao G
微管相关蛋白BRISC通过从NUMA上移除K63连接的多泛素链来调节NUMA与dynein和Importin-β的相互作用，从而促进正确的双极纺锤体组装。脱泛素化酶(DUBS)负向调节蛋白质泛素化，在包括有丝分裂在内的多种生理过程中发挥重要作用。BRCC36异肽酶复合体(BRISC)是赖氨酸63连接的泛素水解酶的特异体，但其生物学功能在很大程度上尚未确定。在这里，我们确定了BRISC在控制培养的哺乳动物细胞有丝分裂纺锤体组装中的关键作用。BRISC是一种与微管(MT)相关的蛋白质复合体，主要定位于K纤维和纺锤体极的负端，并直接与MT结合；重要的是，BRISC通过去泛素化必需的纺锤体组装因子核有丝分裂装置(NUMA)来促进功能性双极纺锤体的组装。NUMA的去泛素化调节其与Dynein和Importin-β的相互作用，这是NUMA在纺锤体组装中发挥功能所必需的。总之，这些结果揭示了BRISC是有丝分裂纺锤体组装和细胞分裂的重要调节因子，并对开发针对BRISC的抗癌药物具有重要意义。
The microtubule-associated protein BRISC regulates the interaction of NuMA with dynein and importin-β by removing K63-linked polyubiquitin chains from NuMA, thereby promoting proper bipolar spindle assembly. Deubiquitinating enzymes (DUBs) negatively regulate protein ubiquitination and play an important role in diverse physiological processes, including mitotic division. The BRCC36 isopeptidase complex (BRISC) is a DUB that is specific for lysine 63–linked ubiquitin hydrolysis; however, its biological function remains largely undefined. Here, we identify a critical role for BRISC in the control of mitotic spindle assembly in cultured mammalian cells. BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs; importantly, BRISC promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). The deubiquitination of NuMA regulates its interaction with dynein and importin-β, which are required for its function in spindle assembly. Collectively, these results uncover BRISC as an important regulator of the mitotic spindle assembly and cell division, and have important implications for the development of anticancer drugs targeting BRISC.