Mammalian Polo-like Kinase 1-dependent Regulation of the PBIP1-CENP-Q Complex at Kinetochores
Mammalian Polo-like Kinase 1-dependent Regulation of the PBIP1-CENP-Q Complex at Kinetochores
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DOI：
10.1074/jbc.m111.224105
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发表时间：
2011-06-03
影响因子：
4.8
通讯作者：
Lee, Kyung S.
中科院分区：
文献类型：
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作者：
Kang, Young H.;Park, Chi-Hoon;Lee, Kyung S.
哺乳动物Polo-like kinase1(Plk1)在M期进程中起着关键作用。PLK1通过C末端Polobox结构域(PBD)的靶向活性定位于特定的亚细胞结构。PBD功能的破坏会导致不正确的两极纺锤体形成、染色体错误分离和胞质分裂缺陷，最终导致非整倍体的产生。已经证明Plk1通过其PBD磷酸化并结合到着丝粒支架PBIP1(也称为MLF1IP和CENP-U[50])而招募到着丝粒。然而，PBIP1本身是如何针对着丝粒的，以及它在调节Plk1依赖的有丝分裂事件中扮演什么角色仍然是未知的。在这里，我们证明了PBIP1与CENP-Q直接相互作用，这种相互作用不仅是它们的稳定性所必需的，也是它们着丝粒定位所必需的。PLK1似乎不与CENP-Q直接相互作用。然而，Plk1通过在PBIP1上自生成p-T78基序与PBIP1和CENP-Q形成三元复合体。这种复合体的形成是依赖Plk1的PBIP1结合的CENP-Q的磷酸化和PBIP1-CENP-Q复合体从有丝分裂着丝粒离域的中心。这项研究揭示了PBIP1如何将Plk1依赖的磷酸化事件介导到第三个蛋白质上的独特机制，并为Plk1及其招募支架PBIP1-CENP-Q复合体定位和非定位于着丝粒的机制提供了新的见解。
Mammalian polo-like kinase 1 (Plk1) plays a pivotal role during M-phase progression. Plk1 localizes to specific subcellular structures through the targeting activity of the C-terminal polobox domain (PBD). Disruption of the PBD function results in improper bipolar spindle formation, chromosome missegregation, and cytokinesis defect that ultimately lead to the generation of aneuploidy. It has been shown that Plk1 recruits itself to centromeres by phosphorylating and binding to a centromere scaffold, PBIP1 (also called MLF1IP and CENP-U[ 50]) through its PBD. However, how PBIP1 itself is targeted to centromeres and what roles it plays in the regulation of Plk1-dependent mitotic events remain unknown. Here, we demonstrated that PBIP1 directly interacts with CENP-Q, and this interaction was mutually required not only for their stability but also for their centromere localization. Plk1 did not appear to interact with CENP-Q directly. However, Plk1 formed a ternary complex with PBIP1 and CENP-Q through a self-generated p-T78 motif on PBIP1. This complex formation was central for Plk1-dependent phosphorylation of PBIP1-bound CENP-Q and delocalization of the PBIP1-CENP-Q complex from mitotic centromeres. This study reveals a unique mechanism of how PBIP1 mediates Plk1-dependent phosphorylation event onto a third protein, and provides new insights into the mechanism of how Plk1 and its recruitment scaffold, PBIP1-CENP-Q complex, are localized to and delocalized from centromeres.