The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II
The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II
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DOI：
10.1101/gad.2016411
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发表时间：
2011-04-15
影响因子：
10.5
通讯作者：
Hirota, Toru
中科院分区：
文献类型：
--
作者：
Abe, Satoshi;Nagasaka, Kota;Hirota, Toru
细胞周期从间期过渡到有丝分裂的最佳特征是出现浓缩的染色体，这些染色体在显微镜下可以在细胞核中看到丝状结构。生物化学上，启动有丝分裂程序需要激活有丝分裂周期蛋白依赖性激酶Cdk1（周期蛋白依赖性激酶1），但Cdk1是否以及如何在有丝分裂进入时触发染色体组装尚不清楚。在这里，我们报道有丝分裂染色体的前期组装依赖于cdk1介导的凝缩蛋白II复合物的磷酸化。我们确定了CAP-D3亚基的Thr 1415是Cdk1磷酸化位点，这被证明是至关重要的，因为Polo激酶Plk1 （Polo样激酶1）需要通过结合CAP-D3定位到染色体轴，从而过度磷酸化凝缩蛋白II复合物。对携带非磷酸化的CAP-D3突变体代替内源性蛋白的细胞的活细胞成像分析表明，Thr 1415的磷酸化是染色体在前期及时凝聚所必需的，而plk1介导的凝聚素II的磷酸化促进了其正确组装染色体的能力。这些观察结果解释了Cdk1如何诱导细胞进入有丝分裂的染色体组装，并强调了Plk1与Cdk1协同作用的重要性。
The cell cycle transition from interphase into mitosis is best characterized by the appearance of condensed chromosomes that become microscopically visible as thread-like structures in nuclei. Biochemically, launching the mitotic program requires the activation of the mitotic cyclin-dependent kinase Cdk1 (cyclin-dependent kinase 1), but whether and how Cdk1 triggers chromosome assembly at mitotic entry are not well understood. Here we report that mitotic chromosome assembly in prophase depends on Cdk1-mediated phosphorylation of the condensin II complex. We identified Thr 1415 of the CAP-D3 subunit as a Cdk1 phosphorylation site, which proved crucial as it was required for the Polo kinase Plk1 (Polo-like kinase 1) to localize to chromosome axes through binding to CAP-D3 and thereby hyperphosphorylate the condensin II complex. Live-cell imaging analysis of cells carrying nonphosphorylatable CAP-D3 mutants in place of endogenous protein suggested that phosphorylation of Thr 1415 is required for timely chromosome condensation during prophase, and that the Plk1-mediated phosphorylation of condensin II facilitates its ability to assemble chromosomes properly. These observations provide an explanation for how Cdk1 induces chromosome assembly in cells entering mitosis, and underscore the significance of the cooperative action of Plk1 with Cdk1.