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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1
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Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker for recruitment of the spindle checkpoint protein Bub1, but not Mad1

机译:中心束缚的Mps1 pombe同源(Mph1)激酶是募集纺锤体检查点蛋白Bub1的足够标记,但不是Mad1的标记

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摘要

The spindle checkpoint delays the onset of anaphase until all of the chromosomes properly achieve bipolar attachment to the spindle. It has been shown that unattached kinetochores are the site that emits a signal for activation of the checkpoint. Although the components of the checkpoint such as Bub1, Mad1 and Mad2 selectively accumulate at unattached kinetochores, the answer to how they recognize unattached kinetochores has remained elusive. Mps1 pombe homolog (Mph1) kinase has been shown to function upstream of most of the components of the checkpoint and thus it is thought to recognize unattached kinetochores by itself and recruit other components. In this study we have expressed a fusion protein of Mph1 and Ndc80 (a kinetochore protein of the outer plate) and shown that the fusion protein arrests cell cycle progression in a spindle-checkpoint-dependent manner in fission yeast. When expression of Mad2 is turned off, the cells grow normally with Mph1 constitutively localized at centromeres/ kinetochores. Under this condition, Bub1 can be found with Mph1 throughout the cell cycle, indicating that localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1. In contrast, Mad1 is found to transiently localize at kinetochores, which are presumably unattached to the spindle, but soon it dissociates from kinetochores. We propose that Mph1 is a sufficient marker for recruitment of Bub1. Mad1, in contrast, requires an additional condition/component for stable association with kinetochores.
机译:纺锤体检查点延迟后期的开始,直到所有染色体都正确地达到纺锤体的双极附着。已经表明,未连接的动植物是发出用于激活检查点的信号的位置。尽管检查点的组件(例如Bub1,Mad1和Mad2)选择性地堆积在未连接的动植物上,但如何识别未连接的动植物的答案仍然难以捉摸。 Mps1 pombe同系物(Mph1)激酶已被证明在检查点大多数组件的上游起作用,因此人们认为它可以自行识别未连接的动植物,并募集其他组件。在这项研究中,我们已经表达了Mph1和Ndc80的融合蛋白(外板的动粒蛋白),并表明该融合蛋白在裂变酵母中以纺锤体检查点依赖性的方式阻止细胞周期的进程。当Mad2的表达关闭时,细胞正常生长,Mph1组成型定位于着丝粒/动植物。在这种条件下,在整个细胞周期中都可以发现Bub1与Mph1结合,表明Mph1在着丝粒/动线粒体的定位足以招募Bub1。相比之下,发现Mad1瞬时定位在动植物上,该动植物可能未附着在纺锤体上,但很快就与动植物分离。我们建议Mph1是Bub1募集的充分标记。相比之下,Mad1需要其他条件/组件才能与动植物稳定关联。

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    Graduate School of Biostudies and Radiation Biology Center, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;

    Graduate School of Biostudies and Radiation Biology Center, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;

    Graduate School of Biostudies and Radiation Biology Center, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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