TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases
TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases
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DOI：
10.1038/ncb1646
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发表时间：
2007-11-01
影响因子：
21.3
通讯作者：
Nurse, Paul
中科院分区：
文献类型：
--
作者：
Petersen, Janni;Nurse, Paul
生长与细胞周期进程的耦合使真核细胞能够根据营养的可获得性以特定的大小分裂。在分裂酵母中，这种偶联涉及SPc1/Sty1丝裂原活化蛋白激酶(MAPK)途径，通过Polo激酶重新聚集到纺锤体极体(SPBS)。在这里，我们报告了营养物质的变化影响TOR信号，而TOR信号调节SPc1/Sty1的活性。雷帕霉素诱导的TOR抑制信号提前有丝分裂开始，模拟在转移到贫乏氮源后细胞分裂时的尺寸缩小。GCN2是TOR信号的效应者和翻译的调节者，它调节Pyp2磷酸酶，进而调节SPc1/Sty1的活性。雷帕霉素或营养素诱导的SPc1/Sty1活性刺激促进Polo激酶SPB的募集和CDc2的激活，从而提前有丝分裂的开始。在GCN2、Pyp2或SPc1/Sty1缺失的细胞中，或阻断SPc1/Sty1依赖的Polo SPB募集时，这种高级有丝分裂的开始被取消。因此，TOR信号通过Pyp2磷酸酶通过应激MAPK途径调节有丝分裂的启动。
The coupling of growth to cell cycle progression allows eukaryotic cells to divide at particular sizes depending on nutrient availability. In fission yeast, this coupling involves the Spc1/Sty1 mitogen-activated protein kinase ( MAPK) pathway working through Polo kinase recruitment to the spindle pole bodies ( SPBs). Here we report that changes in nutrients influence TOR signalling, which modulates Spc1/Sty1 activity. Rapamycin-induced inhibition of TOR signalling advanced mitotic onset, mimicking the reduction in cell size at division seen after shifts to poor nitrogen sources. Gcn2, an effector of TOR signalling and modulator of translation, regulates the Pyp2 phosphatase that in turn modulates Spc1/Sty1 activity. Rapamycin-or nutrient-induced stimulation of Spc1/Sty1 activity promotes Polo kinase SPB recruitment and Cdc2 activation to advance mitotic onset. This advanced mitotic onset is abolished in cells depleted of Gcn2, Pyp2, or Spc1/Sty1 or on blockage of Spc1/Sty1-dependent Polo SPB recruitment. Therefore, TOR signalling modulates mitotic onset through the stress MAPK pathway via the Pyp2 phosphatase.