The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.

The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.
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小分子黄质蛋白揭示了Aurora B在校正动型微管附着和维持纺锤体组装检查点方面的作用。

DOI:
10.1083/jcb.200208092
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发表时间:
2003-04-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Peters JM
Peters JM
中科院分区:
其他
文献类型:
--
作者:
Hauf S;Cole RW;LaTerra S;Zimmer C;Schnapp G;Walter R;Heckel A;van Meel J;Rieder CL;Peters JM

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姐妹染色单体在有丝分裂中的正确分离依赖于所有染色体与纺锤体的双极连接。我们已经确定了小分子橙皮苷作为染色体排列和分离的抑制剂。我们的数据表明橙皮苷通过抑制有丝分裂激酶Aurora B的功能而引起这种表型。用橙皮苷处理的哺乳动物细胞在存在许多单向染色体的情况下进入后期,其中许多染色体可能具有连接到一个纺锤体极的两个姐妹动粒(syntelic attachment)。橙皮苷还可使被紫杉醇或monastrol阻滞的细胞在<1小时内进入后期,而诺考达唑中的细胞可保持阻滞3-5小时。总之,我们的数据表明,极光B是需要在单取向染色体上产生未连接的动粒,这反过来又可以促进双极连接以及维持检查点信号。
The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3–5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.
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