Powers T, Walter P
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco, California 94143-0448, USA.
Mol Biol Cell. 1999 Apr;10(4):987-1000. doi: 10.1091/mbc.10.4.987.
The TOR (target of rapamycin) signal transduction pathway is an important mechanism by which cell growth is controlled in all eucaryotic cells. Specifically, TOR signaling adjusts the protein biosynthetic capacity of cells according to nutrient availability. In mammalian cells, one branch of this pathway controls general translational initiation, whereas a separate branch specifically regulates the translation of ribosomal protein (r-protein) mRNAs. In Saccharomyces cerevisiae, the TOR pathway similarly regulates general translational initiation, but its specific role in the synthesis of ribosomal components is not well understood. Here we demonstrate that in yeast control of ribosome biosynthesis by the TOR pathway is surprisingly complex. In addition to general effects on translational initiation, TOR exerts drastic control over r-protein gene transcription as well as the synthesis and subsequent processing of 35S precursor rRNA. We also find that TOR signaling is a prerequisite for the induction of r-protein gene transcription that occurs in response to improved nutrient conditions. This induction has been shown previously to involve both the Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways, and our results therefore suggest that these three pathways may be intimately linked.
雷帕霉素靶蛋白（TOR）信号转导通路是所有真核细胞中控制细胞生长的重要机制。具体而言，TOR信号根据营养物质的可利用性来调节细胞的蛋白质生物合成能力。在哺乳动物细胞中，该通路的一个分支控制一般的翻译起始，而另一个独立分支则专门调节核糖体蛋白（r蛋白）mRNA的翻译。在酿酒酵母中，TOR通路同样调节一般的翻译起始，但其在核糖体成分合成中的具体作用尚不清楚。在此，我们证明在酵母中，TOR通路对核糖体生物合成的控制惊人地复杂。除了对翻译起始的一般影响外，TOR还对r蛋白基因转录以及35S前体rRNA的合成和后续加工施加严格控制。我们还发现，TOR信号是响应营养条件改善而发生的r蛋白基因转录诱导的先决条件。先前已表明这种诱导涉及Ras-腺苷酸环化酶以及可发酵生长培养基诱导的通路，因此我们的结果表明这三条通路可能紧密相连。
