Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast.
Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast.
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DOI：
10.1016/j.cub.2009.06.043
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发表时间：
2009-07-28
期刊：
影响因子：
--
通讯作者：
Biggins S
中科院分区：
文献类型：
--
作者：
Pinsky BA;Nelson CR;Biggins S
准确的染色体分离依赖于姐妹动粒从相反的两极与微管进行双向连接时受到的张力。纺锤体检查点响应于在产生适当的附着或着丝粒上的张力中的缺陷而停止细胞周期，尽管触发检查点的精确信号尚不清楚，因为张力和附着是耦合的。检查点的靶点是Cdc 20蛋白，其启动后期抑制剂Pds 1/securin的后期促进复合物（APC）依赖性降解。虽然纺锤体检查点激活的分子细节仍在阐明中，但至少四种激酶的磷酸化是一个至关重要的要求。然而，很少有人知道的机制，沉默的检查点一旦动粒双定向。在这里，我们表明，芽殖酵母蛋白磷酸酶I，Glc 7的催化亚基，调节退出检查点。Glc 7过表达阻止响应张力和附着缺陷的纺锤体检查点激活。虽然glc 7突变细胞能够有效地从非检查点介导的中期停滞中释放，但由于纺锤体检查点退出失败，它们对瞬时纺锤体检查点激活非常敏感。因此，我们认为PP 1活性通过逆转关键的磷酸化事件来沉默检查点。
Accurate chromosome segregation depends on sister kinetochores coming under tension when they make bioriented attachments to microtubules from opposite poles. The spindle checkpoint halts the cell cycle in response to defects in generating proper attachments or tension on kinetochores, although the precise signal that triggers the checkpoint is unclear because tension and attachment are coupled. The target of the checkpoint is the Cdc20 protein that initiates the anaphase promoting complex (APC)-dependent degradation of the anaphase inhibitor Pds1/securin. Although the molecular details of spindle checkpoint activation are still being elucidated, phosphorylation by at least four kinases is a crucial requirement. However, less is known about the mechanisms that silence the checkpoint once kinetochores biorient. Here, we show that the catalytic subunit of the budding yeast protein phosphatase I, Glc7, regulates exit from the checkpoint. Glc7 overexpression prevents spindle checkpoint activation in response to both tension and attachment defects. Although glc7 mutant cells are able to efficiently release from a non-checkpoint-mediated metaphase arrest, they are uniquely sensitive to transient spindle checkpoint activation due to a failure in spindle checkpoint exit. We therefore propose that PP1 activity silences the checkpoint by reversing key phosphorylation events.
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影响因子：
9.2
作者：
Minshull, J;Straight, A;Murray, AW
通讯作者：
Murray, AW
DOI：
10.1083/jcb.200710019
发表时间：
2008-04-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Emanuele MJ;Lan W;Jwa M;Miller SA;Chan CS;Stukenberg PT
通讯作者：
Stukenberg PT
影响因子：
7.8
作者：
RIEDER, CL;SCHULTZ, A;SLUDER, G
通讯作者：
SLUDER, G
影响因子：
10.5
作者：
Bloecher, A;Tatchell, K
通讯作者：
Tatchell, K
影响因子：
--
作者：
Poddar, A;Stukenberg, PT;Burke, DJ
通讯作者：
Burke, DJ