Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
Deregulated human Cdc14A phosphatase disrupts centrosome separation and chromosome segregation
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DOI：
10.1038/ncb777
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发表时间：
2002-04-01
影响因子：
21.3
通讯作者：
Lukas, J
中科院分区：
文献类型：
--
作者：
Mailand, N;Lukas, C;Lukas, J
我们发现人类Cdc14A磷酸酶（1）与间期中心体相互作用，这种相互作用不依赖于微管和Cdc14A磷酸酶活性，但需要活跃的核输出。破坏核输出信号（内斯）导致Cdc 14 A定位于核仁，而在未受干扰的细胞中，核仁选择性地含有Cdc 14 B（参考文献1）。有条件的过度生产的Cdc14A，但不是它的磷酸酶死亡或NES缺陷的突变体，或Cdc14B，导致过早的中心体分裂和形成多余的有丝分裂纺锤体。与此相反，下调内源性Cdc14A短抑制RNA双链体（siRNA）诱导有丝分裂缺陷，包括受损的中心体分离和未能进行生产性胞质分裂。因此，过度表达和下调Cdc14A引起异常染色体分配到子细胞。这些结果表明，Cdc14A是一个生理调节中心体复制周期，当中断，可以导致哺乳动物细胞基因组的不稳定性。
We show that human Cdc14A phosphatase(1) interacts with interphase centrosomes, and that this interaction is independent of microtubules and Cdc14A phosphatase activity, but requires active nuclear export. Disrupting the nuclear export signal (NES) led to Cdc14A being localized in nucleoli, which in unperturbed cells selectively contain Cdc14B (ref. 1). Conditional overproduction of Cdc14A, but not its phosphatase-dead or NES-deficient mutants, or Cdc14B, resulted in premature centrosome splitting and formation of supernumerary mitotic spindles. In contrast, downregulation of endogenous Cdc14A by short inhibitory RNA duplexes (siRNA) induced mitotic defects including impaired centrosome separation and failure to undergo productive cytokinesis. Consequently, both overexpression and downregulation of Cdc14A caused aberrant chromosome partitioning into daughter cells. These results indicate that Cdc14A is a physiological regulator of the centrosome duplication cycle, which, when disrupted, can lead to genomic instability in mammalian cells.