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首页> 外文期刊>Molecular biology of the cell >Phosphatase Inhibitor-2 Balances Protein Phosphatase 1 and Aurora B Kinase for Chromosome Segregation and Cytokinesis in Human Retinal Epithelial Cells
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Phosphatase Inhibitor-2 Balances Protein Phosphatase 1 and Aurora B Kinase for Chromosome Segregation and Cytokinesis in Human Retinal Epithelial Cells

机译：磷酸酶抑制剂2平衡蛋白质磷酸酶1和Aurora B激酶在人类视网膜上皮细胞中的染色体分离和胞质分裂

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Mitosis in Saccharomyces cerevisiae depends on IPL1 kinase, which genetically interacts with GLC8. The metazoan homologue of GLC8 is inhibitor-2 (I-2), but its function is not understood. We found endogenous and ectopic I-2 localized to the spindle, midzone, and midbody of mitotic human epithelial ARPE-19 cells. Knockdown of I-2 by RNA interference produced multinucleated cells, with supernumerary centrosomes, multipolar spindles and lagging chromosomes during anaphase. These defects did not involve changes in levels of protein phosphatase-1 (PP1), and the multinuclear phenotype was rescued by overexpression of I-2. Appearance of multiple nuclei and supernumerary centrosomes required progression through the cell cycle and I-2 knockdown cells failed cytokinesis, as observed by time-lapse microscopy. Inhibition of Aurora B by hesperadin produced multinucleated cells and reduced H3S10 phosphorylation. I-2 knockdown enhanced this latter effect. Partial knockdown of PP1Cα prevented multiple nuclei caused by either knockdown of I-2 or treatment with hesperadin. Expression of enhanced green fluorescent protein-I-2 or hemagglutinin-I-2 made cells resistant to hesperadin. We propose that I-2 acts to enhance Aurora B by inhibiting specific PP1 holoenzymes that dephosphorylate Aurora B substrates necessary for chromosome segregation and cytokinesis. Conserved together throughout eukaryotic evolution, I-2, PP1 and Aurora B function interdependently during mitosis.
机译：酿酒酵母中的有丝分裂取决于IPL1激酶，后者与GLC8发生遗传相互作用。 GLC8的后生同源物是抑制剂2（I-2），但其功能尚不清楚。我们发现内源性和异位I-2定位于有丝分裂的人类上皮ARPE-19细胞的纺锤体，中区和中体。 RNA干扰抑制I-2产生多核细胞，后期有多余的中心体，多极纺锤体和落后染色体。这些缺陷不涉及蛋白磷酸酶-1（PP1）水平的改变，并且通过I-2的过表达挽救了多核表型。延时显微镜观察到，多个核和多余核小体的出现需要在整个细胞周期内进行，I-2敲低的细胞不能进行胞质分裂。橙皮苷抑制Aurora B产生多核细胞并减少H3S10磷酸化。 I-2组合可增强后一种效果。 PP1Cα的部分敲低可防止I-2敲低或用橙皮苷治疗引起的多核。表达增强的绿色荧光蛋白-I-2或血凝素-I-2使细胞对橙皮苷具有抗性。我们建议I-2通过抑制特定的PP1全酶来增强Aurora B，该PP1全酶使染色体分离和胞质分裂所必需的Aurora B底物脱磷酸化。在整个真核进化过程中，I-2，PP1和Aurora B共同保守，在有丝分裂过程中相互依赖。

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