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Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation

机译:Cdk1对CPC的磷酸化促进了染色体的双向性

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摘要

Successful partition of replicated genomes at cell division requires chromosome attachment to opposite poles of mitotic spindle (bi-orientation). Any defects in this regulation bring about chromosomal instability, which may accelerate tumour progression in humans. To achieve chromosome bi-orientation at prometaphase, the chromosomal passenger complex (CPC), composed of catalytic kinase Aurora B and regulatory components (INCENP, Survivin and Borealin), must be localized to centromeres to phosphorylate kinetochore substrates. Although the CPC dynamically changes the subcellular localization, the regulation of centromere targeting is largely unknown. Here we isolated a fission yeast cyclin B mutant defective specifically in chromosome bi-orientation. Accordingly, we identified Cdkl (also known as Cdc2)-cyclin-B-dependent phosphorylation of Survivin. Preventing Survivin phosphorylation impairs centromere CPC targeting as well as chromosome bi-orientation, whereas phosphomimetic Survivin suppresses the bi-orientation defect in the cyclin B mutant. Survivin phosphorylation promotes direct binding with shu-goshin, which we now define as a conserved centromeric adaptor of the CPC. In human cells, the phosphorylation of Borealin has a comparable role. Thus, our study resolves the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdkl-cyclin B in chromosome bi-orientation.
机译:复制的基因组在细胞分裂中的成功分配需要染色体附着在有丝分裂纺锤体的相反两极(双向)。该调节的任何缺陷都会导致染色体不稳定,从而可能加速人类的肿瘤发展。为了在前期阶段实现染色体双向定向,必须将由催化激酶Aurora B和调节成分(INCENP,Survivin和Borealin)组成的染色体乘客复合物(CPC)定位于着丝粒以磷酸化动线粒底物。尽管CPC会动态更改亚细胞的定位,但是着丝粒靶向的调控在很大程度上还是未知的。在这里,我们分离出了一个裂变酵母细胞周期蛋白B突变体,该突变体在染色体双向方向上存在缺陷。因此,我们确定了Survivin的Cdkl(也称为Cdc2)-细胞周期蛋白B依赖性磷酸化。阻止Survivin磷酸化会损害着丝粒的CPC定位以及染色体双向性,而拟磷酸化Survivin会抑制cyclin B突变体的双向性缺陷。 Survivin磷酸化促进与Shu-goshin的直接结合,我们现在将其定义为CPC的保守着丝粒接头。在人体细胞中,Borealin的磷酸化作用相当。因此,我们的研究解决了CPC靶向着丝粒的保守机制,突出了Cdkl-cyclin B在染色体双向取向中的关键作用。

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  • 来源
    《Nature》 |2010年第7316期|P.719-723|共5页
  • 作者单位

    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan;

    rnLaboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan;

    rnLaboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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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