Plk1 promotes nuclear translocation of human Cdc25C during prophase
Plk1 promotes nuclear translocation of human Cdc25C during prophase
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DOI：
10.1093/embo-reports/kvf069
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Toyoshima-Morimoto, F;Taniguchi, E;Nishida, E
细胞核内活跃的M期促进因子（MPF）在细胞分裂前期的积累被认为是协调脊椎动物细胞M期活动的关键。蛋白磷酸酶Cdc25C是MPF的激活剂，在前期进入细胞核以保持MPF在细胞核中的活性。然而，在前期控制Cdc25C核转位的分子机制是未知的。我们发现，磷酸化的丝氨酸残基（Ser198）在人类Cdc25C的核输出信号序列发生在前期，并促进Cdc25C的核定位。我们还表明，Polo样激酶1（Plk1）是负责这种磷酸化和组成型活性Plk1促进Cdc25C的核定位。值得注意的是，突变Cdc25C，其中Ser198被丙氨酸取代仍然在细胞质中，当野生型Cdc25C积累在细胞核中在前期。这些结果表明，Plk1磷酸化Cdc25C的Ser198和调节Cdc25C的核转位在前期。
The nuclear accumulation of active M-phase promoting factor (MPF) during prophase is thought to be essential for coordinating M-phase events in vertebrate cells. The protein phosphatase Cdc25C, an activator of MPF, enters the nucleus to keep MPF active in the nucleus during prophase. However, the molecular mechanisms that control nuclear translocation of Cdc25C during prophase are unknown. We show that phosphorylation of a serine residue (Ser198) in a nuclear export signal sequence of human Cdc25C occurs during prophase and promotes nuclear localization of Cdc25C. We also show that Polo-like kinase 1 (Plk1) is responsible for this phosphorylation and that constitutively active Plk1 promotes nuclear localization of Cdc25C. Remarkably, a mutant Cdc25C in which Ser198 is replaced by alanine remains in the cytoplasm when wild-type Cdc25C accumulates in the nucleus during prophase. These results suggest that Plk1 phosphorylates Cdc25C on Ser198 and regulates nuclear translocation of Cdc25C during prophase.