Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy
Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy
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DOI：
10.1007/s11373-005-0980-0
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发表时间：
2005-01-01
影响因子：
11
通讯作者：
Tang, TK
中科院分区：
文献类型：
--
作者：
Chen, HL;Tang, CJC;Tang, TK
极光激酶正在成为中心体功能、染色体分离和胞质分裂的关键调节因子。我们之前在小鼠精子和卵子中表达的激酶筛选中分离出了 Aurora-C (Aiel)，这是第三种类型的 Aurora 激酶。目前，我们对Aurora-C的精确定位和功能知之甚少。异位表达的 GFP-Aurora-C 的免疫荧光分析表明，Aurora-C 是染色体过客蛋白的新成员，在胞质分裂过程中首先定位于着丝粒，然后定位于中央纺锤体。为了研究 Aurora-C 的潜在作用，我们检查了激酶缺陷 (KD) 突变体 (AurC-KD) 在四环素控制下的 HeLa Tet-Off 细胞中的作用。我们的结果表明，AurC-KD 的过度表达会导致细胞分裂缺陷并诱导多倍体和细胞凋亡。有趣的是，AurC-KD 过表达还抑制 Aurora-B、Bub1 和 BubR1 的着丝粒/动粒定位，减少历史性 H3 磷酸化，并破坏 INCENP 与 Aurora-B 的关联。总之，我们的结果表明 Aurora-C 是一种染色体过客蛋白，可能作为细胞分裂的关键调节因子。
Aurora kinases are emerging as key regulators of centrosome function, chromosome segregation and cytokinesis. We previously isolated Aurora-C (Aiel), a third type of Aurora kinase, in a screen for kinases expressed in mouse sperm and eggs. Currently, we know very little about the precise localization and function of Aurora-C. Immunofluorescence analysis of ectopically expressed GFP-Aurora-C has revealed that Aurora-C is a new member of the chromosomal passenger proteins localizing first to the centromeres and then to the central spindles during cytokinesis. In order to study the potential role of Aurora-C, we examined the effects of a kinase-deficient (KD) mutant (AurC-KD) in HeLa Tet-Off cells under tetracycline control. Our results showed that overexpression of AurC-KD causes defects in cell division and induces polyploidy and apoptosis. Interestingly, AurC-KD overexpression also inhibits centromere/kinetochore localization of Aurora-B, Bub1, and BubR1, reduces historic H3 phosphorylation, and disrupts the association of INCENP with Aurora-B. Together, our results showed that Aurora-C is a chromosomal passenger protein, which may serve as a key regulator in cell division.