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The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression

机译：DNA损伤效应子Chk1激酶在细胞周期进程中调节Cdc14B核仁穿梭。

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摘要

Chk1 is a critical effector of DNA damage checkpoints necessary for the maintenance of chromosome integrity during cell cycle progression. Here we report, that Chk1 co-localized with the nucleolar marker, fibrillarin in response to radiation-induced DNA damage in human cells. Interestingly, in vitro studies using GST pull down assays identified the dual-specificity serine/threonine nucleolar phosphatase Cdc14B as a Chk1 substrate. Furthermore, Chk1, but not a kinase-dead Chk1 control, was shown to phosphorylate Cdc14B using an in vitro kinase assay. Co-immunoprecipitation experiments using exogenous Cdc14B transfected into human cells confirmed the interaction of Cdc14B and Chk1 during cell cycle. In addition, reduction of Chk1 levels via siRNA or UCN-01 treatment demonstrated that Chk1 activation following DNA damage was required for Cdc14B export from the nucleolus. these studies have revealed a novel interplay between Chk1 kinase and Cdc14B phosphatase involving radiation-induced nucleolar shuttling to facilitate error-free cell cycle progression and prevent genomic instability.

机译：Chk1是在细胞周期进程中维持染色体完整性所必需的DNA损伤检查点的关键效应物。在这里我们报告说，Chk1与核仁标记物原纤维蛋白共定位，以响应人类细胞中辐射诱导的DNA损伤。有趣的是，使用GST下拉检测的体外研究确定了双特异性丝氨酸/苏氨酸核仁磷酸酶Cdc14B为Chk1底物。此外，使用体外激酶测定法显示，Chk1，而不是激酶死亡的Chk1对照，磷酸化Cdc14B。使用转染到人类细胞中的外源性Cdc14B进行的免疫共沉淀实验证实了Cdc14B和Chk1在细胞周期中的相互作用。此外，通过siRNA或UCN-01处理降低Chk1水平表明，DNA损伤后Chk1激活是从核仁输出Cdc14B所必需的。这些研究揭示了Chk1激酶和Cdc14B磷酸酶之间的新型相互作用，涉及辐射诱导的核仁穿梭，以促进无错误的细胞周期进程并防止基因组不稳定。

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Peddibhotla, Sirisha; Wei, Zhubo; Papineni, Rao; Lam, Micheal H; Rosen, Jeffrey M; Zhang, Pumin;
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年度 2011
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1. The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression. [J] . Peddibhotla S, Wei Z, Papineni R, Cell cycle . 2011,第4期

机译：DNA损伤效应因子Chk1激酶在细胞周期进程中调节Cdc14B核仁穿梭。
2. Checkpoint kinase 1 (Chki)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints [J] . Navjotsingh Pabla, Kirti Bhatt, Zheng Dong Proceedings of the National Academy of Sciences of the United States of America . 2012,第1期

机译：Checkpoint激酶1（Chki）-short是Chk1的剪接变异体和内源性抑制剂，可调节细胞周期和DNA损伤检查点
3. Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2 [J] . Reinhardt HC, Yaffe MB Current Opinion in Cell Biology . 2009,第2期

机译：响应DNA损伤控制细胞周期的激酶：Chk1，Chk2和MK2
4. A lamin-dependent pathway that regulates nuclear organization, cell cycle progression and germ cell development [C] . Ayelet Margalit, Jun Liu, Alexandra Fridkin, Novartis Foundation symposium on Nuclear organization in development and disease . 2005

机译：调节核组织，细胞周期进展和生殖细胞发展的层压依赖性途径
5. Cell cycle-regulated human DNA helicase B in DNA damage response. [D] . Gu, Jinming. 2005

机译：细胞周期调节的人类DNA解旋酶B在DNA损伤反应中。
6. The DNA damage effector Chk1 kinase regulates Cdc14B nucleolar shuttling during cell cycle progression [O] . Sirisha Peddibhotla, Zhubo Wei, Rao Papineni, 2011

机译：DNA损伤效应子Chk1激酶在细胞周期进程中调节Cdc14B核仁穿梭。
7. Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints [O] . Pabla, Navjotsingh, Bhatt, Kirti, Dong, Zheng 2011

机译：Checkpoint激酶1（Chk1）-short是Chk1的剪接变体和内源性抑制剂，可调节细胞周期和DNA损伤检查点

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