Toyoshima-Morimoto Fumiko, Taniguchi Eri, Nishida Eisuke
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
EMBO Rep. 2002 Apr;3(4):341-8. doi: 10.1093/embo-reports/kvf069. Epub 2002 Mar 15.
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.
有丝分裂前期活性M期促进因子（MPF）的核积累被认为对于协调脊椎动物细胞中的M期事件至关重要。蛋白磷酸酶Cdc25C作为MPF的激活剂，在前期进入细胞核以维持MPF在细胞核中的活性。然而，前期控制Cdc25C核转运的分子机制尚不清楚。我们发现，人类Cdc25C核输出信号序列中的一个丝氨酸残基（Ser198）在前期发生磷酸化，并促进Cdc25C的核定位。我们还表明，Polo样激酶1（Plk1）负责这种磷酸化，并且组成型活性Plk1促进Cdc25C的核定位。值得注意的是，当野生型Cdc25C在前期积累在细胞核中时，Ser198被丙氨酸取代的突变型Cdc25C仍留在细胞质中。这些结果表明，Plk1使Cdc25C的Ser198磷酸化，并在前期调节Cdc25C的核转运。
