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首页> 外文期刊>Molecular biology of the cell >Gravin regulates centrosome function through PLK1
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Gravin regulates centrosome function through PLK1

机译：Gravin通过PLK1调节Centrosome功能

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摘要

We propose to understand how the mitotic kinase PLK1 drives chromosome segregation errors, with a specific focus on Gravin, a PLK1 scaffold. In both three-dimensional primary prostate cancer cell cultures that are prone to Gravin depletion and Gravin short hairpin RNA (shRNA)-treated cells, an increase in cells containing micronuclei was noted in comparison with controls. To examine whether the loss of Gravin affected PLK1 distribution and activity, we utilized photokinetics and a PLK1 activity biosensor. Gravin depletion resulted in an increased PLK1 mobile fraction, causing the redistribution of active PLK1, which leads to increased defocusing and phosphorylation of the mitotic centrosome protein CEP215 at serine-613. Gravin depletion further led to defects in microtubule renucleation from mitotic centrosomes, decreased kinetochore-fiber integrity, increased incidence of chromosome misalignment, and subsequent formation of micronuclei following mitosis completion. Murine Gravin rescued chromosome misalignment and micronuclei formation, but a mutant Gravin that cannot bind PLK1 did not. These findings suggest that disruption of a Gravin-PLK1 interface leads to inappropriate PLK1 activity contributing to chromosome segregation errors, formation of micronuclei, and subsequent DNA damage.
机译：我们建议了解有丝分裂激酶PLK1如何驱动染色体隔离误差，具有特定于Gravin，PLK1支架。在易患砾石耗尽和坟墓短发夹RNA（ShRNA） - 治疗细胞的三维一次前列腺癌细胞培养物中，与对照相比，注意到含有微核细胞的细胞的增加。为了检查Gravin是否影响PLK1分布和活性，我们使用了光动力学和PLK1活性生物传感器。 Gravin耗尽导致PLK1移动级分增加，导致活性PLK1的再分布，这导致丝状中心体蛋白CEP215在丝氨酸-613上的散焦和磷酸化增加。 Gravin耗尽进一步导致微管术中的缺陷来自有丝分裂的中心，降低了酮纤维完整性，染色体未对准的发病率增加，以及随后形成微核的结论完成。小鼠雷林抢救染色体错位和微核形成，但不能结合PLK1的突变蛋黄不。这些发现表明，Gravin-PLK1接口的破坏导致不适当的PLK1活性，有助于染色体的分离误差，形成微核和随后的DNA损伤。

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