The Yeast Tor Signaling Pathway Is Involved in G2/M Transition via Polo-Kinase

The Yeast Tor Signaling Pathway Is Involved in G2/M Transition via Polo-Kinase
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DOI:
10.1371/journal.pone.0002223
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发表时间:
2008-05-21
期刊:
影响因子:
3.7
通讯作者:
Kamada, Yoshiaki
Kamada, Yoshiaki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nakashima, Akio;Maruki, Yoshiko;Kamada, Yoshiaki

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雷帕霉素(Tor)蛋白的靶标在细胞生长中起着核心作用。雷帕霉素抑制细胞生长,促进细胞周期停滞于G1期(G0)。然而,关于Tor是否参与了细胞分裂周期的其他阶段,人们知之甚少。在这里,我们报道了雷帕霉素敏感的Tor复合体1(TORC1)参与了酿酒酵母G2/M的转变。携带编码TORC1基本成分的KOG1(kog1-105)温度敏感等位基因的菌株以及用雷帕霉素处理的酵母细胞显示有丝分裂延迟,G2延长。酵母Polo样激酶CDC5的过表达挽救了Kog1-105细胞的生长缺陷,进而降低了Kog1-105细胞中的CDC5活性。TORC1-2A型磷酸酶途径介导了CDC5的核质转运,这是其正确定位和功能的先决条件。CDC5的C-末端Polo-box结构域在核转位中具有抑制作用。综上所述,我们的结果表明了Tor在细胞周期和增殖调节中的一种新功能。
The target of rapamycin (Tor) protein plays central roles in cell growth. Rapamycin inhibits cell growth and promotes cell cycle arrest at G1 (G0). However, little is known about whether Tor is involved in other stages of the cell division cycle. Here we report that the rapamycin-sensitive Tor complex 1 (TORC1) is involved in G2/M transition in S. cerevisiae. Strains carrying a temperature-sensitive allele of KOG1 (kog1-105) encoding an essential component of TORC1, as well as yeast cell treated with rapamycin show mitotic delay with prolonged G2. Overexpression of Cdc5, the yeast polo-like kinase, rescues the growth defect of kog1-105, and in turn, Cdc5 activity is attenuated in kog1-105 cells. The TORC1-Type2A phosphatase pathway mediates nucleocytoplasmic transport of Cdc5, which is prerequisite for its proper localization and function. The C-terminal polo-box domain of Cdc5 has an inhibitory role in nuclear translocation. Taken together, our results indicate a novel function of Tor in the regulation of cell cycle and proliferation.