PHB2 protects sister-chromatid cohesion in mitosis
PHB2 protects sister-chromatid cohesion in mitosis
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DOI：
10.1016/j.cub.2007.07.009
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发表时间：
2007-08-07
期刊：
影响因子：
9.2
通讯作者：
Fukui, Kiichi
中科院分区：
文献类型：
--
作者：
Takata, Hideaki;Matsunaga, Sachihiro;Fukui, Kiichi
姐妹染色单体之间的结合是有丝分裂中染色体正确分离所必需的。在脊椎动物有丝分裂细胞中，大多数粘着蛋白被从染色体臂上去除[1-4]，但着丝粒粘着蛋白受到shugoshin的保护，直到后期开始[5]。然而，这种保护着丝粒凝聚力的机制还没有很好地理解。在这里，我们表明，抑制素2（PHB 2）参与调节姐妹染色单体凝聚力在HeLa细胞有丝分裂。PHB 2是真核生物中进化上保守的蛋白质，具有多种功能，如转录调节和细胞活力和发育[6-8]。然而，其在有丝分裂中的功能尚未确定。我们发现，RNA干扰（RNAi）的PHB 2的耗竭导致过早的姐妹染色单体分离和缺陷的染色体congression伴随着有丝分裂阻滞纺锤体检查点激活。在没有PHB 2的情况下，在早期有丝分裂期间粘附素从着丝粒解离，尽管shugoshin的着丝粒定位被保留。因此，我们的研究结果表明，除了shugoshin，PHB 2也需要在早期有丝分裂期间保护着丝粒凝聚力免受PIK 1的磷酸化，并且其功能对于适当的有丝分裂进程至关重要。
Cohesion between sister chromatids is essential for proper chromosome segregation in mitosis. In vertebrate mitotic cells, most cohesin is removed from the chromosome arms [1-4], but centromeric cohesin is protected by shugoshin until the onset of anaphase [5]. However, the mechanism of this protection of centromeric cohesion is not well understood. Here, we demonstrate that prohibitin 2 (PHB2) is involved in the regulation of sister-chromatid cohesion during mitosis in HeLa cells. PHB2 is an evolutionarily conserved protein in eukaryotes and has multiple functions, such as transcriptional regulation and cell viability and development [6-8]. However, its functions in mitosis have not yet been determined. We show that depletion of PHB2 by RNA interference (RNAi) causes premature sister-chromatid separation and defects in chromosome congression accompanied by mitotic arrest by spindle-checkpoint activation. In the absence of PHB2, cohesin is dissociated from centromeres during early mitosis, although the centromeric localization of shugoshin is preserved. Thus, our findings suggest that, in addition to the shugoshin, PHB2 is also required to protect the centromeric cohesion from phosphorylation by PIk1 during early mitosis and that its function is essential for proper mitotic progression.