Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing.

Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing.
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DOI:
10.1083/jcb.201205090
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发表时间:
2012-08-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lampson MA
Lampson MA
中科院分区:
其他
文献类型:
--
作者:
Liu D;Davydenko O;Lampson MA

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plk 1动力学在着丝粒控制两个关键的有丝分裂过程:最初建立正确的着丝粒微管附件,随后沉默纺锤体检查点。Polo样激酶-1(Plk 1)是一种高度保守的具有多种有丝分裂功能的激酶。Plk 1定位于前中期着丝粒,并在中期着丝粒减少,类似于许多检查点信号蛋白,但Plk 1不是纺锤体检查点功能所必需的。Plk 1也参与稳定着丝粒微管附件,但这些附件是最稳定的着丝粒Plk 1水平低时,在中期。因此,目前还不清楚如何Plk 1在着丝粒的功能,可以理解其动态定位的背景下。在本文中,我们表明,Plk 1活性抑制动粒微管动力学稳定在前中期的初始附件,和Plk 1从动粒去除是必要的,以保持动态微管中期。组成性靶向Plk 1的动粒保持高活性中期,导致减少interkinetochore张力和intratkinetochore拉伸,检查点依赖的有丝分裂停滞,和积累微管附着错误。总之,我们的数据表明,Plk 1动力学在着丝粒控制两个关键的有丝分裂过程:最初建立正确的着丝粒微管附件,随后沉默纺锤体检查点。
Plk1 dynamics at kinetochores control two critical mitotic processes: initially establishing correct kinetochore–microtubule attachments and subsequently silencing the spindle checkpoint. Polo-like kinase-1 (Plk1) is a highly conserved kinase with multiple mitotic functions. Plk1 localizes to prometaphase kinetochores and is reduced at metaphase kinetochores, similar to many checkpoint signaling proteins, but Plk1 is not required for spindle checkpoint function. Plk1 is also implicated in stabilizing kinetochore–microtubule attachments, but these attachments are most stable when kinetochore Plk1 levels are low at metaphase. Therefore, it is unclear how Plk1 function at kinetochores can be understood in the context of its dynamic localization. In this paper, we show that Plk1 activity suppresses kinetochore–microtubule dynamics to stabilize initial attachments in prometaphase, and Plk1 removal from kinetochores is necessary to maintain dynamic microtubules in metaphase. Constitutively targeting Plk1 to kinetochores maintained high activity at metaphase, leading to reduced interkinetochore tension and intrakinetochore stretch, a checkpoint-dependent mitotic arrest, and accumulation of microtubule attachment errors. Together, our data show that Plk1 dynamics at kinetochores control two critical mitotic processes: initially establishing correct kinetochore–microtubule attachments and subsequently silencing the spindle checkpoint.
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