The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle
The autoregulated instability of Polo-like kinase 4 limits centrosome duplication to once per cell cycle
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DOI：
10.1101/gad.207027.112
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发表时间：
2012-12-15
影响因子：
10.5
通讯作者：
Cleveland, Don W.
中科院分区：
文献类型：
--
作者：
Holland, Andrew J.;Fachinetti, Daniele;Cleveland, Don W.
中心粒组织中心体，准确控制中心粒的数量对于维持基因组完整性至关重要。中心粒复制每个细胞周期发生一次，并由 Polo 样激酶 4 (Plk4) 控制。我们之前表明 Plk4 自身磷酸化以促进其被蛋白酶体降解。在这里，我们证明这种自动调节的不稳定性控制着内源性 Plk4 的丰度。阻止 Plk4 的自动调节会导致中心体扩增、p53 稳定以及细胞增殖丧失；此外，抑制p53可使携带扩增中心体的细胞生长。因此，Plk4 自动调节通过将中心体复制限制在每个细胞周期一次来防止基因组不稳定。
Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centriole duplication occurs once per cell cycle and is controlled by Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradation by the proteasome. Here we demonstrate that this autoregulated instability controls the abundance of endogenous Plk4. Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation; moreover, suppression of p53 allows growth of cells carrying amplified centrosomes. Plk4 autoregulation thus guards against genome instability by limiting centrosome duplication to once per cell cycle.