Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos.

Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos.
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DOI:
10.1083/jcb.201408064
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发表时间:
2015-03-16
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Pintard L
Pintard L
中科院分区:
其他
文献类型:
--
作者:
Tavernier N;Noatynska A;Panbianco C;Martino L;Van Hove L;Schwager F;Léger T;Gotta M;Pintard L

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Cdk 1对SPAT-1/Bora的磷酸化增强了Aurora A对Plk 1的磷酸化,并促进了C.优美的动物发育过程中有丝分裂进入的分子机制还不完全清楚。在这里,我们表明,有丝分裂激酶CDK-1磷酸化抑制蛋白Par-Two 1(SPAT-1)/Bora调节其与PLK-1的相互作用,并触发有丝分裂进入早期秀丽隐杆线虫胚胎。胚胎表达SPAT-1的版本是nonphosphorylatable由CDK-1和PLK-1的结合在体外是有缺陷的有丝分裂进入延迟,模仿胚胎缺乏SPAT-1或PLK-1的功能。我们进一步表明,磷酸化SPAT-1激活PLK-1触发磷酸化T环在体外由极光A。同样,我们发现Cdk 1对人Bora的磷酸化促进Aurora A对人Plk 1的磷酸化,这表明这种机制在人类中是保守的。我们的结果表明CDK-1通过SPAT-1磷酸化激活PLK-1以促进进入有丝分裂。我们提出了一个正反馈回路的存在,连接Cdk 1和Plk 1激活,以确保有丝分裂进入和细胞分裂时间的鲁棒控制。
Phosphorylation of SPAT-1/Bora by Cdk1 enhances Plk1 phosphorylation by Aurora A and promotes entry into mitosis in C. elegans. The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho–SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing.
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