Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability.
Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability.
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DOI：
10.1038/ncomms11117
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发表时间：
2016-03-31
影响因子：
16.6
通讯作者：
Maehara Y
中科院分区：
文献类型：
--
作者：
Iimori M;Watanabe S;Kiyonari S;Matsuoka K;Sakasai R;Saeki H;Oki E;Kitao H;Maehara Y
微管动力学的时间调控对于有丝分裂的正常进行是必不可少的，而通过磷酸化控制微管正端跟踪蛋白是这种调控的重要组成部分。本研究表明，极光B和CDK1在氨基端多个位点磷酸化微管末端结合蛋白2 (EB2)，并在连接钙钙蛋白同源和末端结合同源结构域的连接物中磷酸化一簇丝氨酸/苏氨酸残基。与有丝分裂进入和进展密切相关的EB2磷酸化降低了EB2对微管的结合亲和力。非磷酸化EB2的表达诱导稳定的着丝点微管动力学，并以微管结合依赖的方式延迟双极中期板的形成，即使在未受干扰的有丝分裂中也会导致非整倍性。我们认为，极光B和CDK1暂时调节EB2对微管的结合亲和力，从而确保着丝点微管动力学、适当的有丝分裂进程和基因组稳定性。有丝分裂中微管动力学的时间调控可以通过微管正端蛋白的磷酸化来实现。在这里，作者发现Aurora B和CDK1磷酸化EB2，从而改变微管结合亲和力，控制着丝粒微管动力学和基因组稳定性。
Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability. Temporal regulation of microtubule dynamics in mitosis can be achieved by phosphorylation of microtubule plus-end proteins. Here, the authors show that Aurora B and CDK1 phosphorylate EB2, which changes microtubule binding affinity and controls kinetochore microtubule dynamics and genome stability.