首页> 美国卫生研究院文献>Molecular Cellular Proteomics : MCP >Proteomic Analysis of the Mammalian Katanin Family of Microtubule-severing Enzymes Defines Katanin p80 subunit B-like 1 (KATNBL1) as a Regulator of Mammalian Katanin Microtubule-severing
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Proteomic Analysis of the Mammalian Katanin Family of Microtubule-severing Enzymes Defines Katanin p80 subunit B-like 1 (KATNBL1) as a Regulator of Mammalian Katanin Microtubule-severing

机译:蛋白质组学分析的哺乳动物肾小管切断微囊切断酶家族定义了肝丹宁p80亚基B样1(KATNBL1)作为哺乳动物肾小管切断微管调节剂。

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摘要

The Katanin family of microtubule-severing enzymes is critical for remodeling microtubule-based structures that influence cell division, motility, morphogenesis and signaling. Katanin is composed of a catalytic p60 subunit (A subunit, KATNA1) and a regulatory p80 subunit (B subunit, KATNB1). The mammalian genome also encodes two additional A-like subunits (KATNAL1 and KATNAL2) and one additional B-like subunit (KATNBL1) that have remained poorly characterized. To better understand the factors and mechanisms controlling mammalian microtubule-severing, we have taken a mass proteomic approach to define the protein interaction module for each mammalian Katanin subunit and to generate the mammalian Katanin family interaction network (Katan-ome). Further, we have analyzed the function of the KATNBL1 subunit and determined that it associates with KATNA1 and KATNAL1, it localizes to the spindle poles only during mitosis and it regulates Katanin A subunit microtubule-severing activity in vitro. Interestingly, during interphase, KATNBL1 is sequestered in the nucleus through an N-terminal nuclear localization signal. Finally KATNB1 was able to compete the interaction of KATNBL1 with KATNA1 and KATNAL1. These data indicate that KATNBL1 functions as a regulator of Katanin A subunit microtubule-severing activity during mitosis and that it likely coordinates with KATNB1 to perform this function.
机译:Katanin家族的微管切断酶对于重塑影响细胞分裂,运动性,形态发生和信号传导的微管结构至关重要。 Katanin由催化性p60亚基(A亚基,KATNA1)和调节性p80亚基(B亚基,KANTB1)组成。哺乳动物基因组还编码了两个附加的A-样亚基(KATNAL1和KATNAL2)和一个附加的B-样亚基(KATNBL1),这些亚基的特征仍然很差。为了更好地了解控制哺乳动物微管切断的因素和机制,我们采取了蛋白质组学方法来定义每个哺乳动物Katanin亚基的蛋白质相互作用模块并生成哺乳动物Katanin家族相互作用网络(Katan-ome)。此外,我们已经分析了KATNBL1亚基的功能,并确定它与KATNA1和KATNAL1相关,仅在有丝分裂期间定位于纺锤极,并且在体外调节Katanin A亚基微管的切割活性。有趣的是,在相间期,KATNBL1通过N端核定位信号被隔离在核中。最终,KATNB1能够竞争KATNBL1与KATNA1和KATNAL1的相互作用。这些数据表明,KATNBL1在有丝分裂过程中起着Katanin A亚基微管切割活性的调节剂的作用,并且很可能与KATNB1协同作用来执行此功能。

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