The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
Exp Cell Res. 2012 Nov 1;318(18):2344-52. doi: 10.1016/j.yexcr.2012.07.001. Epub 2012 Jul 20.
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 kinase 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.
肌动蛋白三联体相关重复序列（Tara）是一种 F-actin 结合蛋白，可调节肌动蛋白细胞骨架的组织。在我们之前的研究中，我们发现 Tara 与端粒重复结合因子 1（TRF1）相互作用，并介导 TRF1 在有丝分裂调控中的功能。我们还发现，HECTD3 的过表达，一种 HECT E3 泛素连接酶的成员，增强了 Tara 的体内泛素化，并促进了 Tara 的降解，这种 Tara 的降解促进了细胞周期的进展。然而，关于 Tara 在有丝分裂中的翻译后修饰知之甚少。在这里，我们表明 Tara 是一种新型的 Polo 样激酶 1（Plk1）靶蛋白。Plk1 在体内和体外与 Tara 相互作用并磷酸化它。实际上，Tara 上的 Thr-457 是 Plk1 的一个真正的体内磷酸化位点。有趣的是，我们发现 Tara 的中心体定位依赖于 Thr-457 磷酸化和 Plk1 的激酶活性。此外，过表达非磷酸化突变型的 Tara 会导致 HeLa 细胞有丝分裂异常延迟。我们的研究表明，Plk1 介导的磷酸化依赖的 Tara 中心体定位对于准确的染色体分离是重要的，并为理解 Plk1 在与 Tara 合作促进有丝分裂进程中的作用提供了新的见解。
