The TOR signaling cascade regulates gene expression in response to nutrients
The TOR signaling cascade regulates gene expression in response to nutrients
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DOI：
10.1101/gad.13.24.3271
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发表时间：
1999-12-15
影响因子：
10.5
通讯作者：
Heitman, J
中科院分区：
文献类型：
--
作者：
Cardenas, ME;Cutler, NS;Heitman, J
雷帕霉素抑制TOR激酶，TOR激酶调节细胞增殖和mRNA翻译，并且从酵母到人类是保守的。TOR激酶还调节对营养物质的反应，包括孢子形成、自噬、交配和核糖体生物发生。我们使用代表整个酵母基因组的阵列分析了暴露于雷帕霉素的酵母细胞中的基因表达。雷帕霉素抑制TOR可诱导由Ure2抑制因子和转录调节因子Gln3控制的氮源利用基因的表达，全面抑制核糖体蛋白的表达。gln3突变导致雷帕霉素耐药，而ure2突变导致雷帕霉素超敏，甚至在表达显性雷帕霉素耐药TOR突变的细胞中也是如此。我们发现，在体内，Ure2是一种磷酸化蛋白，在雷帕霉素或氮限制下会迅速去磷酸化。总之，我们的研究结果表明，TOR级联除了在调节翻译、核糖体生物发生和氨基酸渗透酶稳定性方面发挥已知作用外，还在调节营养响应的转录方面发挥重要作用。
Rapamycin inhibits the TOR kinases, which regulate cell proliferation and mRNA translation and are conserved from yeast to man. The TOR kinases also regulate responses to nutrients, including sporulation, autophagy, mating, and ribosome biogenesis. We have analyzed gene expression in yeast cells exposed to rapamycin using arrays representing the whole yeast genome. TOR inhibition by rapamycin induces expression of nitrogen source utilization genes controlled by the Ure2 repressor and the transcriptional regulator Gln3, and globally represses ribosomal protein expression. gln3 mutations were found to confer rapamycin resistance, whereas ure2 mutations confer rapamycin hypersensitivity, even in cells expressing dominant rapamycin-resistant TOR mutants. We find that Ure2 is a phosphoprotein in vivo that is rapidly dephosphorylated in response to rapamycin or nitrogen limitation. In summary, our results reveal that the TOR cascade plays a prominent role in regulating transcription in response to nutrients in addition to its known roles in regulating translation, ribosome biogenesis, and amino acid permease stability.