Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres
Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres
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DOI：
10.1101/gad.1945310
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发表时间：
2010-10-01
影响因子：
10.5
通讯作者：
Watanabe, Yoshinori
中科院分区：
文献类型：
--
作者：
Tanno, Yuji;Kitajima, Tomoya S.;Watanabe, Yoshinori
Shugoshin（Sgo）是一种保守的着丝粒蛋白。哺乳动物Sgo 1与蛋白磷酸酶2A（PP 2A）合作保护有丝分裂粘附素免于前期解离途径。尽管另一种shugoshin样蛋白Sgo 2是生殖细胞中着丝粒保护凝聚力所必需的，但其精确的分子功能在很大程度上仍然是难以捉摸的。我们表明，hSgo 2在染色体congression和着丝粒保护的凝聚力在HeLa细胞中起着双重作用，而后者的功能只暴露在扰动有丝分裂。这些功能部分重叠与极光B，激酶设置忠实的染色体分离。因此，我们鉴定了Aurora B在N-末端卷曲螺旋区域和中间区域对hSgo 2的磷酸化，并表明这些磷酸化分别促进hSgo 2与PP 2A和MCAK的结合，PP 2A和MCAK分别是着丝粒保护和染色体组装所需的因子。此外，这些磷酸化对于将PP 2A和MCAK定位于着丝粒是必需的。这种机制似乎也适用于生殖细胞。因此，我们的研究确定Sgo 2作为迄今为止未知的极光B在哺乳动物细胞中的重要细胞底物。
Shugoshin (Sgo) is a conserved centromeric protein. Mammalian Sgo1 collaborates with protein phosphatase 2A (PP2A) to protect mitotic cohesin from the prophase dissociation pathway. Although another shugoshin-like protein, Sgo2, is required for the centromeric protection of cohesion in germ cells, its precise molecular function remains largely elusive. We demonstrate that hSgo2 plays a dual role in chromosome congression and centromeric protection of cohesion in HeLa cells, while the latter function is exposed only in perturbed mitosis. These functions partly overlap with those of Aurora B, a kinase setting faithful chromosome segregation. Accordingly, we identified the phosphorylation of hSgo2 by Aurora B at the N-terminal coiled-coil region and the middle region, and showed that these phosphorylations separately promote binding of hSgo2 to PP2A and MCAK, factors required for centromeric protection and chromosome congression, respectively. Furthermore, these phosphorylations are essential for localizing PP2A and MCAK to centromeres. This mechanism seems applicable to germ cells as well. Thus, our study identifies Sgo2 as a hitherto unknown crucial cellular substrate of Aurora B in mammalian cells.