Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis
Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis
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DOI：
10.1038/cr.2008.11
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发表时间：
2008-02-01
期刊：
影响因子：
44.1
通讯作者：
Zhang, Chuamnao
中科院分区：
文献类型：
--
作者：
Chen, Qiang;Zhang, Xiaoyan;Zhang, Chuamnao
细胞周期蛋白B1是脊椎动物细胞周期进程的关键调控蛋白。细胞周期蛋白B1与细胞周期蛋白依赖性激酶催化亚基CDK1结合，形成一个复合物，通过关键蛋白的磷酸化来协调有丝分裂。Cyclin B1调节CDK1的激活及其亚细胞定位，这可能对底物选择至关重要。在此，我们证明细胞周期蛋白B1在前期集中在着丝点的外板上。这种定位需要蛋白质的周期蛋白盒区。细胞周期蛋白B1通过附着在着丝点上的微管从单个着丝点转移到纺锤极，这种转移依赖于动力蛋白/动力蛋白复合物。细胞周期蛋白B1被基于载体的siRNA耗尽导致着丝点和微管之间的低效附着，染色体排列缺陷，并延迟后期的开始。我们得出结论，细胞周期蛋白B1在前期的着丝点积累，在那里它有助于微管与着丝点的正确连接和染色体的有效排列，最有可能是通过细胞周期蛋白B1- cdk1对特定底物的局部磷酸化。当微管附着完成后，细胞周期蛋白B1从每个着丝点运输，这种重新定位可能会改变细胞周期蛋白B1- cdk1的活性，并导致纺锤体组装检查点失活。
Cyclin B1 is a key regulatory protein controlling cell cycle progression in vertebrates. Cyclin B1 binds,CDK1, a cyclin-dependent kinase catalytic subunit, forming a complex that orchestrates mitosis through phosphorylation of key proteins. Cyclin B1 regulates both the activation of CDK1 and its subcellular localization, which may be critical for substrate selection. Here, we demonstrate that cyclin B1 is concentrated on the outer plate of the kinetochore during prometaphase. This localization requires the cyclin box region of the protein. Cyclin B1 is displaced from individual kinetochores to the spindle poles by microtubule attachment to the kinetochores, and this displacement is dependent on the dynein/dynactin complex. Depletion of cyclin B1 by vector-based siRNA causes inefficient attachment between kinetochores and microtubules, and chromosome alignment defects, and delays the onset of anaphase. We conclude that cyclin B1 accumulates at kinetochores during prometaphase, where it contributes to the correct attachment of microtubules to kinetochores and efficient alignment of the chromosomes, most likely through localized phosphorylation of specific substrates by cyclin B1-CDK1. Cyclin B1 is then transported from each kinetochore as microtubule attachment is completed, and this relocalization may redirect the activity of cyclin B1-CDK1 and contribute to inactivation of the spindle assembly checkpoint.