Aurora A kinase modulates actin cytoskeleton through phosphorylation of Cofilin: Implication in the mitotic process.

Aurora A kinase regulates early mitotic events through phosphorylation and activation of a variety of proteins. Specifically, Aur-A is involved in centrosomal separation and formation of mitotic spindles in early prophase. The effect of Aur-A on mitotic spindles is mediated by the modulation of microtubule dynamics and association with microtubule binding proteins. In this study we show that Aur-A exerts its effects on spindle organization through the regulation of the actin cytoskeleton. Aurora A phosphorylates Cofilin at multiple sites including S3 resulting in the inactivation of its actin depolymerizing function. Aur-A interacts with Cofilin in early mitotic phases and regulates its phosphorylation status. Cofilin phosphorylation follows a dynamic pattern during the progression of prophase to metaphase. Inhibition of Aur-A activity induced a delay in the progression of prophase to metaphase. Aur-A inhibitor also disturbed the pattern of Cofilin phosphorylation, which correlated with the mitotic delay. Our results establish a novel function of Aur-A in the regulation of actin cytoskeleton reorganization, through Cofilin phosphorylation during early mitotic stages.

极光激酶A通过磷酸化和激活多种蛋白质来调控早期有丝分裂事件。具体而言，极光激酶A在早前期参与中心体分离和有丝分裂纺锤体的形成。极光激酶A对有丝分裂纺锤体的作用是通过调节微管动力学以及与微管结合蛋白的结合来介导的。在本研究中，我们表明极光激酶A通过调节肌动蛋白细胞骨架对纺锤体组织产生影响。极光激酶A在包括S3在内的多个位点磷酸化丝切蛋白，导致其肌动蛋白解聚功能失活。极光激酶A在有丝分裂早期与丝切蛋白相互作用并调节其磷酸化状态。在前期到中期的进展过程中，丝切蛋白的磷酸化呈现动态模式。抑制极光激酶A的活性会导致前期到中期进展延迟。极光激酶A抑制剂也扰乱了丝切蛋白的磷酸化模式，这与有丝分裂延迟相关。我们的研究结果确立了极光激酶A在有丝分裂早期阶段通过丝切蛋白磷酸化来调节肌动蛋白细胞骨架重组的一种新功能。