PP2A is required for centromeric localization of sgol and proper chromosome segregation
PP2A is required for centromeric localization of sgol and proper chromosome segregation
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DOI：
10.1016/j.devcel.2006.03.010
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发表时间：
2006-05-01
影响因子：
11.8
通讯作者：
Yu, Hongtao
中科院分区：
文献类型：
--
作者：
Tang, Zhanyun;Shu, Hongjun;Yu, Hongtao
姐妹染色单体凝聚力的丧失触发有丝分裂中的染色体分离，并且在脊椎动物细胞中通过两种机制发生：（1）在前期期间，通过有丝分裂激酶（包括PIK 1）磷酸化和从染色体臂去除凝聚素，以及（2）在Meta-后期转换时通过分离酶切割着丝粒凝聚素。Bub 1和MEI-S332/Shugoshin（Sgo 1）蛋白家族在前期保护着丝粒粘附素免受有丝分裂激酶的影响。我们发现，人Sgo 1结合蛋白磷酸酶2A（PP 2A）。PP 2A以Bub 1依赖的方式定位于着丝粒。Sgo 1-PP 2A相互作用是Sgo 1在人类细胞中的着丝粒定位和正确的染色体分离所必需的。通过RNA干扰（RNAi）消除PIK 1恢复了Sgo 1的着丝粒定位，并防止PP2A_A α缺失的细胞中的染色体错误分离。我们的研究结果表明，Bub 1的目标PP 2A的着丝粒，这反过来又保持在着丝粒Sgo 1通过抵消PIK 1介导的染色体删除Sgo 1。
Loss of sister-chromatid cohesion triggers chromosome segregation in mitosis and occurs through two mechanisms in vertebrate cells: (1) phosphorylation and removal of cohesin from chromosome arms by mitotic kinases, including PIk1, during prophase, and (2) cleavage of centromeric cohesin by separase at the meta phase-anaphase transition. Bub1 and the MEI-S332/Shugoshin (Sgo1) family of proteins protect centromeric cohesin from mitotic kinases during prophase. We show that human Sgo1 binds to protein phosphatase 2A (PP2A). PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1-PP2A interaction is required for centromeric localization of Sgo1 and proper chromosome segregation in human cells. Depletion of PIk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_A alpha. Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting PIK1-mediated chromosome removal of Sgo1.