Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores.
Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores.
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DOI：
10.1016/j.cub.2012.03.052
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发表时间：
2012-05-22
期刊：
影响因子：
9.2
通讯作者：
Biggins, Sue
中科院分区：
文献类型：
--
作者：
London, Nitobe;Ceto, Steven;Ranish, Jeffrey A.;Biggins, Sue
着丝粒是与微管相互作用以介导染色体分离的大分子复合物。准确的分离要求动粒从相反的两极双向附着到微管上。着丝粒和微管之间的连接由纺锤体检查点监控，这是一种监视系统，可以防止分裂后期，直到每对染色体都进行正确的双向连接。检查点活性与检查点蛋白向动粒的募集相关。MPS 1是一种保守的蛋白激酶，调节分离和纺锤体检查点，但很少有介导其功能的靶点已被确定。在这里，我们表明，Mps 1是主要的激酶活性，共纯化与芽殖酵母动粒颗粒，并确定保守的Spc 105/KNL-1/Blinkin动粒蛋白作为底物。Spc 105内保守的MELT基序的磷酸化将Bub 1蛋白招募到着丝粒，这被蛋白磷酸酶I（PP 1）逆转。缺乏Mps 1磷酸化位点的Spc 105突变体在纺锤体检查点有缺陷，并表现出生长缺陷。总之，这些数据确定Spc 105作为Mps 1激酶的关键靶标，并表明Mps 1和PP 1的相反活性调节Bub 1蛋白的动粒定位。
Kinetochores are the macromolecular complexes that interact with microtubules to mediate chromosome segregation. Accurate segregation requires that kinetochores make bioriented attachments to microtubules from opposite poles. Attachments between kinetochores and microtubules are monitored by the spindle checkpoint, a surveillance system that prevents anaphase until every pair of chromosomes makes proper bioriented attachments. Checkpoint activity is correlated with the recruitment of checkpoint proteins to the kinetochore. Mps1 is a conserved protein kinase that regulates segregation and the spindle checkpoint, but few of the targets that mediate its functions have been identified. Here, we show that Mps1 is the major kinase activity that co-purifies with budding yeast kinetochore particles and identify the conserved Spc105/KNL-1/Blinkin kinetochore protein as a substrate. Phosphorylation of conserved MELT motifs within Spc105 recruits the Bub1 protein to kinetochores and this is reversed by protein phosphatase I (PP1). Spc105 mutants lacking Mps1 phosphorylation sites are defective in the spindle checkpoint and exhibit growth defects. Together, these data identify Spc105 as a key target of the Mps1 kinase and show that the opposing activities of Mps1 and PP1 regulate the kinetochore localization of the Bub1 protein.
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DOI：
10.1074/jbc.m111.307355
发表时间：
2012-02-17
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lee S;Thebault P;Freschi L;Beaufils S;Blundell TL;Landry CR;Bolanos-Garcia VM;Elowe S
通讯作者：
Elowe S
影响因子：
9.2
作者：
Rosenberg, Jessica S.;Cross, Frederick R.;Funabiki, Hironori
通讯作者：
Funabiki, Hironori
DOI：
10.1083/jcb.200902128
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Klebig C;Korinth D;Meraldi P
通讯作者：
Meraldi P
DOI：
10.1016/j.cub.2009.06.043
发表时间：
2009-07-28
期刊：
Current biology : CB
影响因子：
--
作者：
Pinsky BA;Nelson CR;Biggins S
通讯作者：
Biggins S
影响因子：
5.3
作者：
Kerscher, O;Crotti, LB;Basrai, MA
通讯作者：
Basrai, MA