Teleman Aurelio A, Hietakangas Ville, Sayadian Aram C, Cohen Stephen M
EMBL, Meyerhofstrasse 1, Heidelberg, Germany.
Cell Metab. 2008 Jan;7(1):21-32. doi: 10.1016/j.cmet.2007.11.010.
Animals use the insulin/TOR signaling pathway to mediate their response to fluctuations in nutrient availability. Energy and amino acids are monitored at the single-cell level via the TOR branch of the pathway and systemically via insulin signaling to regulate cellular growth and metabolism. Using a combination of genetics, expression profiling, and chromatin immunoprecipitation, we examine nutritional control of gene expression and identify the transcription factor Myc as an important mediator of TOR-dependent regulation of ribosome biogenesis. We also identify myc as a direct target of FOXO and provide genetic evidence that Myc has a key role in mediating the effects of TOR and FOXO on growth and metabolism. FOXO and TOR also converge to regulate protein synthesis, acting via 4E-BP and Lk6, regulators of the translation factor eIF4E. This study uncovers a network of convergent regulation of protein biosynthesis by the FOXO and TOR branches of the nutrient-sensing pathway.
动物利用胰岛素/TOR信号通路来介导它们对营养可利用性波动的反应。能量和氨基酸通过该信号通路的TOR分支在单细胞水平上受到监测，并通过胰岛素信号在全身水平上受到监测，以调节细胞生长和代谢。通过结合遗传学、表达谱分析和染色质免疫沉淀技术，我们研究了基因表达的营养控制，并确定转录因子Myc是TOR依赖性核糖体生物发生调控的重要介导因子。我们还确定Myc是FOXO的直接靶点，并提供遗传学证据表明Myc在介导TOR和FOXO对生长和代谢的影响中起关键作用。FOXO和TOR还通过翻译因子eIF4E的调节因子4E-BP和Lk6共同作用来调节蛋白质合成。这项研究揭示了营养感应信号通路中FOXO和TOR分支对蛋白质生物合成的汇聚调控网络。
