Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
EMBO J. 2012 Aug 29;31(17):3620-34. doi: 10.1038/emboj.2012.224. Epub 2012 Aug 7.
Polarisation of the actin cytoskeleton must cease during cytokinesis, to support efficient assembly and contraction of the actomyosin ring at the site of cell division, but the underlying mechanisms are still understood poorly in most species. In budding yeast, the Mitotic Exit Network (MEN) releases Cdc14 phosphatase from the nucleolus during anaphase, leading to the inactivation of mitotic forms of cyclin-dependent kinase (CDK) and the onset of septation, before G1-CDK can be reactivated and drive re-polarisation of the actin cytoskeleton to a new bud. Here, we show that premature inactivation of mitotic CDK, before release of Cdc14, allows G1-CDK to divert the actin cytoskeleton away from the actomyosin ring to a new site of polarised growth, thereby delaying progression through cytokinesis. Our data indicate that cells normally avoid this problem via the MEN-dependent release of Cdc14, which counteracts all classes of CDK-mediated phosphorylations during cytokinesis and blocks polarised growth. The dephosphorylation of CDK targets is therefore central to the mechanism by which the MEN and Cdc14 initiate cytokinesis and block polarised growth during late mitosis.
有丝分裂后期，纺锤体两极必须解聚，为在细胞分裂位点处装配和收缩肌动球蛋白环提供支持，但大多数物种的这一机制仍不清楚。在出芽酵母中，有丝分裂后期，纺锤体两极解聚时，MEN（Mitotic Exit Network）将 Cdc14 磷酸酶从核仁中释放出来，导致有丝分裂周期蛋白依赖性激酶（CDK）失活和隔膜形成开始，然后 G1-CDK 才能被重新激活，并驱动肌动蛋白细胞骨架重新向新的芽极化。在这里，我们表明，在 Cdc14 释放之前过早失活有丝分裂 CDK，允许 G1-CDK 将肌动蛋白细胞骨架从肌动球蛋白环转移到新的极化生长位点，从而延迟细胞通过胞质分裂的进程。我们的数据表明，细胞通常通过 MEN 依赖性的 Cdc14 释放来避免这个问题，该释放在胞质分裂过程中中和所有 CDK 介导的磷酸化，阻止极化生长。因此，CDK 靶标的去磷酸化是 MEN 和 Cdc14 启动胞质分裂和阻止末期有丝分裂期间极化生长的机制的核心。
