Chen Hua-Ling, Tang Chieh-Ju C, Chen Chiung-Ya, Tang Tang K
Institute of Biomedical Sciences, Academia Sinica, 128, Academia Road, Sec. 2, Taipei, 11529, Taiwan, ROC.
J Biomed Sci. 2005;12(2):297-310. doi: 10.1007/s11373-005-0980-0.
Aurora kinases are emerging as key regulators of centrosome function, chromosome segregation and cytokinesis. We previously isolated Aurora-C (Aie1), 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 histone 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.
极光激酶正逐渐成为中心体功能、染色体分离和胞质分裂的关键调节因子。我们之前在对小鼠精子和卵子中表达的激酶进行的筛选中分离出了极光激酶C（Aie1），这是极光激酶的第三种类型。目前，我们对极光激酶C的确切定位和功能了解甚少。对异位表达的绿色荧光蛋白 - 极光激酶C进行的免疫荧光分析表明，极光激酶C是染色体乘客蛋白的新成员，在胞质分裂期间首先定位于着丝粒，然后定位于中央纺锤体。为了研究极光激酶C的潜在作用，我们在四环素控制下检测了激酶缺陷（KD）突变体（AurC - KD）对HeLa Tet - Off细胞的影响。我们的结果表明，AurC - KD的过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的过表达还会抑制极光激酶B、Bub1和BubR1在着丝粒/动粒的定位，降低组蛋白H3磷酸化，并破坏INCENP与极光激酶B的结合。总之，我们的结果表明，极光激酶C是一种染色体乘客蛋白，可能是细胞分裂中的关键调节因子。
