Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins
Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins
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DOI：
10.1073/pnas.96.26.14866
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Hardwick, JS;Kuruvilla, FG;Schreiber, SL
免疫抑制剂雷帕霉素抑制 Tor1p 和 Tor2p（雷帕霉素蛋白的靶标），最终通过涉及翻译停滞的机制导致营养剥夺特征的细胞反应。我们测量了在丰富培养基中生长并用雷帕霉素处理的酵母的即时转录反应，以研究 Tor 蛋白对营养敏感信号通路的直接影响。结果表明，Tor 蛋白直接调节葡萄糖激活和氮辨别途径以及响应二元转变的途径（包括糖酵解和柠檬酸循环）。 Tor 蛋白不直接调节一般氨基酸控制、氮饥饿或孢子形成（在二倍体细胞中）途径。氮质量差会激活氮辨别途径，该途径由转录抑制子 Ure2p 和激活子 Gln3p 的复合物控制。用雷帕霉素抑制 Tor 蛋白会增加 Ure2p 的电泳迁移率。这里介绍的工作说明了基于基因组和生化方法的协调使用来描绘由小分子的蛋白质靶点调节的细胞途径。
The immunosuppressant rapamycin inhibits Tor1p and Tor2p (target of rapamycin proteins), ultimately resulting in cellular responses characteristic of nutrient deprivation through a mechanism involving translational arrest. We measured the immediate transcriptional response of yeast grown in rich media and treated with rapamycin to investigate the direct effects of Tor proteins on nutrient-sensitive signaling pathways. The results suggest that Tor proteins directly modulate the glucose activation and nitrogen discrimination pathways and the pathways that respond to the diauxic shift (including glycolysis and the citric acid cycle). Tor proteins do not directly modulate the general amino acid control, nitrogen starvation, or sporulation (in diploid cells) pathways. Poor nitrogen quality activates the nitrogen discrimination pathway, which is controlled by the complex of the transcriptional repressor Ure2p and activator Gln3p. Inhibiting Tor proteins with rapamycin increases the electrophoretic mobility of Ure2p. The work presented here illustrates the coordinated use of genome-based and biochemical approaches to delineate a cellular pathway modulated by the protein target of a small molecule.