Barbet N C, Schneider U, Helliwell S B, Stansfield I, Tuite M F, Hall M N
Department of Biochemistry, University of Basel, Switzerland.
Mol Biol Cell. 1996 Jan;7(1):25-42. doi: 10.1091/mbc.7.1.25.
Saccharomyces cerevisiae cells treated with the immunosuppressant rapamycin or depleted for the targets of rapamycin TOR1 and TOR2 arrest growth in the early G1 phase of the cell cycle. Loss of TOR function also causes an early inhibition of translation initiation and induces several other physiological changes characteristic of starved cells entering stationary phase (G0). A G1 cyclin mRNA whose translational control is altered by substitution of the UBI4 5' leader region (UBI4 is normally translated under starvation conditions) suppresses the rapamycin-induced G1 arrest and confers starvation sensitivity. These results suggest that the block in translation initiation is a direct consequence of loss of TOR function and the cause of the G1 arrest. We propose that the TORs, two related phosphatidylinositol kinase homologues, are part of a novel signaling pathway that activates eIF-4E-dependent protein synthesis and, thereby, G1 progression in response to nutrient availability. Such a pathway may constitute a checkpoint that prevents early G1 progression and growth in the absence of nutrients.
用免疫抑制剂雷帕霉素处理的酿酒酵母细胞,或雷帕霉素靶标TOR1和TOR2缺失的细胞,会在细胞周期的G1早期阶段停止生长。TOR功能的丧失还会导致翻译起始的早期抑制,并诱导进入静止期(G0)的饥饿细胞的其他几种生理变化。一种G1细胞周期蛋白mRNA,其翻译控制通过替换UBI4 5'前导区而改变(UBI4通常在饥饿条件下翻译),可抑制雷帕霉素诱导的G1期停滞并赋予饥饿敏感性。这些结果表明,翻译起始的阻断是TOR功能丧失的直接后果,也是G1期停滞的原因。我们提出,TORs这两个相关的磷脂酰肌醇激酶同系物,是一种新型信号通路的一部分,该通路激活依赖eIF-4E的蛋白质合成,从而响应营养物质的可用性促进G1期进程。这样的通路可能构成一个检查点,在缺乏营养物质时阻止G1期的早期进程和生长。