Dynamic Phosphorylation of NudC by Aurora B in Cytokinesis.
Dynamic Phosphorylation of NudC by Aurora B in Cytokinesis.
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DOI：
10.1371/journal.pone.0153455
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yu-Lee LY
中科院分区：
文献类型：
--
作者：
Weiderhold KN;Fadri-Moskwik M;Pan J;Nishino M;Chuang C;Deeraksa A;Lin SH;Yu-Lee LY
核分布蛋白C（NudC）是一种在胞质分裂中起作用的有丝分裂调节因子。然而，NudC在胞质分裂过程中是如何调节的仍不清楚。在这里，我们表明，NudC是磷酸化的极光B，激酶的关键细胞凋亡。NudC与Aurora B共定位于中间体，并在有丝分裂中与Aurora B共免疫沉淀。ZM 447439对Aurora B的抑制降低了NudC的磷酸化，表明NudC是体内Aurora B的底物。我们鉴定了NudC上的T40作为极光B磷酸化位点。NudC缺失导致胞质分裂失败，子细胞之间的细胞间桥显著延长，持续的中间体极光B活性，并减少细胞分裂。这些细胞动力学缺陷可以通过野生型NudC的异位表达来挽救。发现用T40A磷酸缺陷型NudC重建可挽救胞质分裂缺陷。相反，用T40D磷酸模拟物NudC重建在支持胞质分裂的完成方面是低效的。这些结果表明Aurora B对NudC的动态磷酸化调节胞质分裂。
Nuclear distribution protein C (NudC) is a mitotic regulator that plays a role in cytokinesis. However, how NudC is regulated during cytokinesis remains unclear. Here, we show that NudC is phosphorylated by Aurora B, a kinase critical for cell abscission. NudC is co-localized with Aurora B at the midbody and co-immunoprecipitated with Aurora B in mitosis. Inhibition of Aurora B by ZM447439 reduced NudC phosphorylation, suggesting that NudC is an Aurora B substrate in vivo. We identified T40 on NudC as an Aurora B phosphorylation site. NudC depletion resulted in cytokinesis failure with a dramatic elongation of the intercellular bridge between daughter cells, sustained Aurora B activity at the midbody, and reduced cell abscission. These cytokinetic defects can be rescued by the ectopic expression of wild-type NudC. Reconstitution with T40A phospho-defective NudC was found to rescue the cytokinesis defect. In contrast, reconstitution with the T40D phospho-mimetic NudC was inefficient in supporting the completion of cytokinesis. These results suggest that that dynamic phosphorylation of NudC by Aurora B regulates cytokinesis.