CENP-U Cooperates with Hec1 to Orchestrate Kinetochore-Microtubule Attachment
CENP-U Cooperates with Hec1 to Orchestrate Kinetochore-Microtubule Attachment
复制标题
CENP-U 与 Hec1 合作协调动粒-微管附着
DOI：
10.1074/jbc.m110.174946
复制
发表时间：
2011-01-14
影响因子：
4.8
通讯作者：
Yao, Xuebiao
中科院分区：
文献类型：
--
作者：
Hua, Shasha;Wang, Zhikai;Yao, Xuebiao
有丝分裂是染色体和纺锤体微管之间动态相互作用的协调，通过这种相互作用，基因组物质被平均分配到两个子细胞中。先前的研究表明，CENP-U 是染色体正确分离所必需的组成性着丝粒成分。然而，精确的分子机制仍然难以捉摸。在这里，我们确定 CENP-U 是 Hec1 的新型相互作用伙伴，Hec1 是一种进化上保守的动粒核心成分，对染色体可塑性至关重要。 shRNA 抑制 CENP-U 会导致有丝分裂缺陷，动粒-微管附着受损。有趣的是，CENP-U不仅直接结合微管，而且在体外表现出与Hec1协同微管结合活性。此外，我们还表明 CENP-U 是 Aurora-B 的底物。重要的是，CENP-U 的磷酸化会导致着丝粒-微管相互作用减少，从而有助于 Aurora-B 的纠错功能。综上所述，我们的结果表明 CENP-U 是一种新型微管结合蛋白，并通过与 Hec1 的相互作用在动粒-微管附着中发挥重要作用。
Mitosis is an orchestration of dynamic interaction between chromosomes and spindle microtubules by which genomic materials are equally distributed into two daughter cells. Previous studies showed that CENP-U is a constitutive centromere component essential for proper chromosome segregation. However, the precise molecular mechanism has remained elusive. Here, we identified CENP-U as a novel interacting partner of Hec1, an evolutionarily conserved kinetochore core component essential for chromosome plasticity. Suppression of CENP-U by shRNA resulted in mitotic defects with an impaired kinetochore-microtubule attachment. Interestingly, CENP-U not only binds microtubules directly but also displays a cooperative microtubule binding activity with Hec1 in vitro. Furthermore, we showed that CENP-U is a substrate of Aurora-B. Importantly, phosphorylation of CENP-U leads to reduced kinetochore-microtubule interaction, which contributes to the error-correcting function of Aurora-B. Taken together, our results indicate that CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1.