Phosphorylation of Tara by Plk1 is essential for faithful chromosome segregation in mitosis
Phosphorylation of Tara by Plk1 is essential for faithful chromosome segregation in mitosis
复制标题
Plk1 对 Tara 的磷酸化对于有丝分裂中染色体的忠实分离至关重要。
DOI：
10.1016/j.yexcr.2012.07.001
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发表时间：
2012-11-01
影响因子：
3.7
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Zhu, Yuanyuan;Wang, Chong;Huang, He
肌动蛋白三相关重复序列（塔拉）是一种F-肌动蛋白结合蛋白，调节肌动蛋白细胞骨架结构。在我们以前的研究中，我们发现塔拉与端粒重复序列结合因子1（TRF 1）相关，并介导TRF 1在有丝分裂调控中的功能。我们还发现，HECT E3泛素连接酶的成员HECTD 3的过表达增强了体内塔拉的泛素化并促进了塔拉的降解，并且这种塔拉的降解促进了细胞周期的进展。然而，对塔拉在有丝分裂中的翻译后修饰知之甚少。在这里，我们表明，塔拉是一个新的Polo样lcinase 1（Plk 1）的目标蛋白。Plk 1在体内和体外与塔拉相互作用并使其磷酸化。实际上，塔拉中的Thr-457是Plk 1真正的体内磷酸化位点。有趣的是，我们发现塔拉的中心体定位依赖于Thr-457磷酸化和Plk 1的激酶活性。此外，过表达塔拉的非磷酸化突变体导致HeLa细胞中异常的有丝分裂延迟。我们的研究表明，Plk 1介导的磷酸依赖性中心体定位的塔拉是重要的忠实的染色体分离，并提供了新的见解，了解Plk 1在有丝分裂过程中的作用与塔拉合作。(C)2012 Elsevier Inc. All rights reserved.
Trio-associated repeat on actin (Tara) is an F-actin binding protein and regulates actin cytoskeletal organization. In our previous study, we have found that Tara associates with telomeric repeat binding factor 1 (TRF1) and mediates the function of TRF1 in mitotic regulation. We also found that overexpression HECTD3, a member of HECT E3 ubiquitin ligases, enhances the ubiquitination of Tara in vivo and promotes the degradation of Tara, and such degradation of Tara facilitates cell cycle progression. However, less is known about the post-translational modification of Tara in mitosis. Here we show that Tara is a novel Polo-like lcinase 1 (Plk1) target protein. Plk1 interacts with and phosphorylates Tara in vivo and in vitro. Actually, the Thr-457 in Tara was a bona fide in vivo phosphorylation site for Plk1. Interestingly, we found that the centrosomal localization of Tara depended on the Thr-457 phosphorylation and the kinase activity of Plk1. Furthermore, overexpression of non-phosphorylatable mutant of Tara caused aberrant mitosis delay in HeLa cells. Our study demonstrated that Plk1-mediated phospho-dependent centrosomal localization of Tara is important for faithful chromosome segregation, and provided novel insights into understanding on the role of Plk1 in cooperation with Tara in mitotic progression. (C) 2012 Elsevier Inc. All rights reserved.