Plk1-mediated mitotic phosphorylation of PinX1 regulates its stability.
Plk1-mediated mitotic phosphorylation of PinX1 regulates its stability.
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DOI：
10.1016/j.ejcb.2010.05.005
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发表时间：
2010-10
影响因子：
6.6
通讯作者：
Chong Wang;Jian Yu;Kai Yuan;Jianping Lan;Changjiang Jin;He Huang
中科院分区：
文献类型：
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作者：
Chong Wang;Jian Yu;Kai Yuan;Jianping Lan;Changjiang Jin;He Huang
PinX 1最初被鉴定为Pin 2/TRF 1相互作用蛋白，其通过其端粒酶抑制结构域（TID）抑制端粒酶活性并调节TRF 1在端粒酶阳性细胞中的核仁定位。除了其端粒定位，PinX 1还可以在人类细胞的核仁中发现。我们最近的研究表明，PinX 1定位于有丝分裂的染色体外周和动粒。PinX 1的缺失导致有丝分裂中的落后染色体和间期的微核。然而，很少有人知道PinX 1在有丝分裂中的翻译后修饰。在这里，我们表明，Polo样激酶1（Plk 1）是一种新的相互作用蛋白的PinX 1。Plk 1在体内和体外与PinX 1相互作用并磷酸化PinX 1。Plk 1的过表达促进PinX 1的蛋白质周转，这一过程依赖于泛素相关的蛋白酶体降解。使用siRNA去除Plk 1增加了PinX 1在有丝分裂中蛋白质水平的稳定性。此外，Plk 1介导的PinX 1在5个磷酸化位点的磷酸化是必不可少的Plk 1诱导的降解。这些结果表明，Plk 1可能通过有丝分裂磷酸化负调控PinX 1的稳定性。
PinX1 was originally identified as a Pin2/TRF1-interacting protein that suppresses telomerase activity via its telomerase inhibitor domain (TID) and regulates the nucleolar localization of TRF1 in telomerase-positive cells. In addition to its telomeric localization, PinX1 can be found in the nucleoli of human cells. Our recent studies have shown that PinX1 localizes to the chromosome periphery and kinetochores in mitosis. Depletion of PinX1 results in lagging chromosomes in mitosis and micronuclei in interphase. However, less is known about the post-translational modification of PinX1 in mitosis. Here, we show that Polo-like kinase 1 (Plk1) is a novel interacting protein of PinX1. Plk1 interacts with and phosphorylates PinX1 in vivo and in vitro. Overexpression of Plk1 promotes protein turnover of PinX1, a process that depends on ubiquitin-associated proteasomal degradation. Depletion of Plk1 using siRNA increases the stability of PinX1 at protein level in mitosis. Moreover, Plk1-mediated phosphorylation of PinX1 at five phosphorylation sites is essential for its Plk1-induced degradation. These findings suggest that Plk1 may negatively regulate the stability of PinX1 by mitotic phosphorylation.