Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores.
Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores.
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DOI：
10.1083/jcb.200208091
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发表时间：
2003-04-28
期刊：
影响因子：
--
通讯作者：
Taylor SS
中科院分区：
文献类型：
--
作者：
Ditchfield C;Johnson VL;Tighe A;Ellston R;Haworth C;Johnson T;Mortlock A;Keen N;Taylor SS
Aurora/Ipl1蛋白激酶家族在有丝分裂和胞质分裂中发挥多种作用。在这里，我们描述了一种新的选择性极光激酶抑制剂ZM447439。ZM447439处理的细胞进入间期，正常进入有丝分裂，并组装成双极纺锤体。然而，染色体配对、分离和胞质分裂都失败了。尽管存在定向错误的染色体，ZM447439处理的细胞仍以正常的动力学方式退出有丝分裂，表明纺锤体检查点受到损害。事实上，ZM447439可以防止紫杉醇引起的有丝分裂停滞。RNA干扰实验表明，这些表型是由于Aurora B的抑制，而不是Aurora A或其他某种激酶的抑制。在缺乏Aurora B功能的情况下，纺锤体检查点组件BubR1、MAD2和CENP-E的动粒局部化程度降低。此外，抑制Aurora B激酶活性可阻止BubR1在着丝粒张力降低后与中期着丝粒重新结合。Aurora B激酶活性也是BubR1进入有丝分裂时的磷酸化所必需的。最后，我们证明了BubR1不仅是纺锤体检查点功能所必需的，也是染色体配对所必需的。综上所述，这些结果表明，通过将检查点蛋白靶向动点中心，Aurora B将染色体与后期开始对齐。
The Aurora/Ipl1 family of protein kinases plays multiple roles in mitosis and cytokinesis. Here, we describe ZM447439, a novel selective Aurora kinase inhibitor. Cells treated with ZM447439 progress through interphase, enter mitosis normally, and assemble bipolar spindles. However, chromosome alignment, segregation, and cytokinesis all fail. Despite the presence of maloriented chromosomes, ZM447439-treated cells exit mitosis with normal kinetics, indicating that the spindle checkpoint is compromised. Indeed, ZM447439 prevents mitotic arrest after exposure to paclitaxel. RNA interference experiments suggest that these phenotypes are due to inhibition of Aurora B, not Aurora A or some other kinase. In the absence of Aurora B function, kinetochore localization of the spindle checkpoint components BubR1, Mad2, and Cenp-E is diminished. Furthermore, inhibition of Aurora B kinase activity prevents the rebinding of BubR1 to metaphase kinetochores after a reduction in centromeric tension. Aurora B kinase activity is also required for phosphorylation of BubR1 on entry into mitosis. Finally, we show that BubR1 is not only required for spindle checkpoint function, but is also required for chromosome alignment. Together, these results suggest that by targeting checkpoint proteins to kinetochores, Aurora B couples chromosome alignment with anaphase onset.
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DOI：
10.1083/jcb.43.1.40
发表时间：
1969-10
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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DOI：
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影响因子：
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10.1073/pnas.081076898
发表时间：
2001-04-10
影响因子：
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Adams, RR;Carmena, M;Earnshaw, WC
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