The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells
The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells
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DOI：
10.4161/cc.7.9.5792
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发表时间：
2008-05-01
期刊：
影响因子：
4.3
通讯作者：
Jallepalli, Prasad V.
中科院分区：
文献类型：
--
作者：
Berdougo, Eli;Nachury, Maxence V.;Jallepalli, Prasad V.
在酵母中，蛋白磷酸酶Cdc14通过逆转Cdk1催化的m期磷酸化来促进染色体分离、有丝分裂退出和细胞分裂。Cdc14调控的一个关键特征是它在核核内的隔离，这限制了它在细胞周期的大部分时间内接近潜在底物。哺乳动物也具有核仁Cdc14同源物，称为Cdc14B，但其在有丝分裂和细胞分裂中的作用尚不明确。在这里，我们分析了Cdc14B在有丝分裂过程中的亚细胞动力学，并通过对人体细胞中Cdc14B位点的纯合破坏严格测试了其对细胞分裂的功能贡献。虽然Cdc14B最初在有丝分裂开始时从核核中释放出来，但在后期，磷酸酶迅速重新分配到分离的姐妹染色单体上。这种再定位主要是由Cdk1失活驱动的，因为前期中期细胞中Cdk1的药理抑制将Cdc14B重定向到染色体上。然而，与酵母cdc14突变体形成鲜明对比的是，人Cdc14B（Delta/Delta）细胞是有活力的，并且在纺锤体组装、后期进展、有丝分裂退出和细胞分裂方面没有缺陷，并且继续以接近正常的熟练程度分离核糖体DNA重复序列。我们的研究结果揭示了酵母和哺乳动物细胞在有丝分裂调控上的实质性差异，因为后者在缺乏核核cdc14相关磷酸酶的情况下具有完成m期晚期事件的有效机制。
In yeast, the protein phosphatase Cdc14 promotes chromosome segregation, mitotic exit, and cytokinesis by reversing M-phase phosphorylations catalyzed by Cdk1. A key feature of Cdc14 regulation is its sequestration within the nucleolus, which restricts its access to potential substrates for much of the cell cycle. Mammals also possess a nucleolar Cdc14 homolog, termed Cdc14B, but its roles during mitosis and cell division remain speculative. Here we analyze Cdc14B's subcellular dynamics during mitosis and rigorously test its functional contributions to cell division through homozygous disruption of the Cdc14B locus in human somatic cells. While Cdc14B is initially released from nucleoli at the start of mitosis, the phosphatase quickly redistributes onto segregating sister chromatids during anaphase. This relocalization is mainly driven by Cdk1 inactivation, as pharmacologic inhibition of Cdk1 in prometaphase cells redirects Cdc14B onto chromosomes. However, in sharp contrast to yeast cdc14 mutants, human Cdc14B(Delta/Delta) cells were viable and lacked defects in spindle assembly, anaphase progression, mitotic exit, and cytokinesis, and continued to segregate ribosomal DNA repeats with near-normal proficiency. Our findings reveal substantial divergence in mitotic regulation between yeast and mammalian cells, as the latter possess efficient mechanisms for completing late M-phase events in the absence of a nucleolar Cdc14-related phosphatase.