Tavernier Nicolas, Panbianco Costanza, Gotta Monica, Pintard Lionel
a Jacques Monod Institute; UMR7592; Paris-Diderot University; CNRS ; Paris , France.
Cell Cycle. 2015 Aug 3;14(15):2394-8. doi: 10.1080/15384101.2015.1053673. Epub 2015 Jun 3.
Mitosis is orchestrated by several protein kinases including Cdks, Plks and Aurora kinases. Despite considerable progress toward understanding the individual function of these protein kinases, how their activity is coordinated in space and time during mitosis is less well understood. In a recent article published in the Journal of Cell Biology, we show that CDK-1 regulates PLK-1 activity during mitosis in C. elegans embryos through multisite phosphorylation of the PLK-1 activator SPAT-1 (Aurora Borealis, Bora in human). SPAT-1 variants mutated on CDK-1 phosphorylation sites results in severe delays in mitotic entry, mimicking embryos lacking spat-1 or plk-1 function. We further show that SPAT-1 phosphorylation by CDK-1 promotes its binding to PLK-1 and stimulates PLK-1 phosphorylation on its activator T-loop by Aurora A kinase in vitro. Likewise, we find that phosphorylation of Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A suggesting that this mechanism is conserved in humans. These results indicate that Cdk1 regulates Plk1 by boosting its kinase activity. Here we discuss these recent findings and open questions regarding the regulation of Plk1/PLK-1 by Cdk1/CDK-1 and Bora/SPAT-1.
有丝分裂由包括周期蛋白依赖性激酶（Cdks）、Polo样激酶（Plks）和极光激酶在内的多种蛋白激酶协调调控。尽管在理解这些蛋白激酶的个体功能方面取得了相当大的进展，但它们在有丝分裂过程中的活性如何在空间和时间上协调仍不太清楚。在最近发表于《细胞生物学杂志》的一篇文章中，我们表明，在秀丽隐杆线虫胚胎的有丝分裂过程中，周期蛋白依赖性激酶1（CDK-1）通过对极光激酶B的激活因子SPAT-1（在人类中为北极光激酶Bora）进行多位点磷酸化来调节Polo样激酶1（PLK-1）的活性。在CDK-1磷酸化位点发生突变的SPAT-1变体导致有丝分裂起始严重延迟，类似于缺乏spat-1或plk-1功能的胚胎。我们进一步表明，CDK-1对SPAT-1的磷酸化促进了它与PLK-1的结合，并在体外刺激极光激酶A对PLK-1激活环上的磷酸化。同样，我们发现Cdk1对Bora的磷酸化促进了极光激酶A对人类Plk1的磷酸化，这表明这种机制在人类中是保守的。这些结果表明，Cdk1通过增强Plk1的激酶活性来对其进行调控。在此，我们讨论这些最新发现以及关于Cdk1/CDK-1和Bora/SPAT-1对Plk1/PLK-1调控的开放性问题。
