Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.
Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.
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DOI：
10.1083/jcb.201001006
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发表时间：
2010-03-22
期刊：
影响因子：
--
通讯作者：
Lampson MA
中科院分区：
文献类型：
--
作者：
Liu D;Vleugel M;Backer CB;Hori T;Fukagawa T;Cheeseman IM;Lampson MA
KNL将PP 1靶向到着丝粒，在那里它拮抗极光B活性。着丝粒和纺锤体微管之间的相互作用对维持染色体分离过程中基因组的稳定性至关重要。极光B激酶磷酸化动粒底物，使动粒-微管相互作用不稳定，并消除不正确的附着。这些底物必须被去磷酸化以稳定正确的连接，但相对的激酶和磷酸酶活性如何在动粒处协调尚不清楚。在这里，我们证明了一个保守的基序在动粒蛋白KNL 1直接相互作用，并针对蛋白磷酸酶1（PP 1）的外部动粒。KNL 1的PP 1募集需要使着丝粒处的Aurora B底物去磷酸化并稳定微管附着。着丝粒的PP 1水平受到调节，并与局部极光B活性成反比。事实上，我们证明，极光B磷酸化KNL 1破坏KNL 1-PP 1的相互作用。总之，我们的研究结果支持一个正反馈机制，极光B活动在着丝粒不仅直接针对基板，但也防止本地化的对立磷酸酶。
KNL targets PP1 to kinetochores, where it antagonizes Aurora B activity. Regulated interactions between kinetochores and spindle microtubules are essential to maintain genomic stability during chromosome segregation. The Aurora B kinase phosphorylates kinetochore substrates to destabilize kinetochore–microtubule interactions and eliminate incorrect attachments. These substrates must be dephosphorylated to stabilize correct attachments, but how opposing kinase and phosphatase activities are coordinated at the kinetochore is unknown. Here, we demonstrate that a conserved motif in the kinetochore protein KNL1 directly interacts with and targets protein phosphatase 1 (PP1) to the outer kinetochore. PP1 recruitment by KNL1 is required to dephosphorylate Aurora B substrates at kinetochores and stabilize microtubule attachments. PP1 levels at kinetochores are regulated and inversely proportional to local Aurora B activity. Indeed, we demonstrate that phosphorylation of KNL1 by Aurora B disrupts the KNL1–PP1 interaction. In total, our results support a positive feedback mechanism by which Aurora B activity at kinetochores not only targets substrates directly, but also prevents localization of the opposing phosphatase.
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DOI：
10.1016/j.cub.2008.08.012
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期刊：
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