Mitotic Regulation by NEK Kinase Networks.

Mitotic Regulation by NEK Kinase Networks.
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DOI:
10.3389/fcell.2017.00102
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发表时间:
2017
影响因子:
5.5
通讯作者:
Roig J
Roig J
中科院分区:
生物学2区
文献类型:
--
作者:
Fry AM;Bayliss R;Roig J

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在酵母和果蝇的遗传学研究中,发现细胞周期蛋白依赖性激酶(CDKs)、polo样激酶(PLKs)和Aurora激酶是有丝分裂的重要调节因子。这些酶已经在大多数真核生物中被发现,它们的细胞周期相关功能被详细地描述了。然而,对另一种真菌物种——细粒曲霉(Aspergillus nidulans)的遗传研究发现了一个独特的蛋白激酶家族——NEKs,它也被广泛保守,在细胞周期中起着关键作用,但研究得很少。然而,现在清楚的是,多个NEK家族成员在网络中调节有丝分裂的特定事件,包括中心体分离、纺锤体组装和细胞质分裂。在这里,我们描述了我们目前对NEK激酶如何参与这些过程的理解,特别是通过与微管细胞骨架相关的蛋白质的靶向磷酸化。我们还介绍了控制NEKs激活状态的分子事件的最新发现,以及这些事件如何揭示酶调节的新模式,不仅与其他激酶有关,而且与疾病的病理机制有关。
Genetic studies in yeast and Drosophila led to identification of cyclin-dependent kinases (CDKs), Polo-like kinases (PLKs) and Aurora kinases as essential regulators of mitosis. These enzymes have since been found in the majority of eukaryotes and their cell cycle-related functions characterized in great detail. However, genetic studies in another fungal species, Aspergillus nidulans, identified a distinct family of protein kinases, the NEKs, that are also widely conserved and have key roles in the cell cycle, but which remain less well studied. Nevertheless, it is now clear that multiple NEK family members act in networks to regulate specific events of mitosis, including centrosome separation, spindle assembly and cytokinesis. Here, we describe our current understanding of how the NEK kinases contribute to these processes, particularly through targeted phosphorylation of proteins associated with the microtubule cytoskeleton. We also present the latest findings on molecular events that control the activation state of the NEKs and how these are revealing novel modes of enzymatic regulation relevant not only to other kinases but also to pathological mechanisms of disease.
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