Cancer Institute, Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China.
Cell Mol Life Sci. 2013 Aug;70(16):2873-85. doi: 10.1007/s00018-012-1195-y. Epub 2012 Dec 16.
The target of rapamycin (TOR) is a central regulator controlling cell growth. TOR is highly conserved from yeast to mammals, and is deregulated in human cancers and diabetes. TOR complex 1 (TORC1) integrates signals from growth factors, cellular energy status, stress, and amino acids to control cell growth, mitochondrial metabolism, and lipid biosynthesis. The mechanisms of growth factors and cellular energy status in regulating TORC1 have been well established, whereas the mechanism by which amino acid induces TORC1 remains largely unknown. Recent studies revealed that Rag GTPases play a central role in the regulation of TORC1 activation in response to amino acids. In this review, we will discuss the recent progress in our understanding of Rag GTPase-regulated TORC1 activation in response to amino acids. Particular focus will be given to the function of Rag GTPases in TORC1 activation and how Rag GTPases are regulated by amino acids.
雷帕霉素靶蛋白(TOR)是一种控制细胞生长的核心调节剂。TOR 在从酵母到哺乳动物的过程中高度保守,并且在人类癌症和糖尿病中失调。TOR 复合物 1(TORC1)整合了来自生长因子、细胞能量状态、应激和氨基酸的信号,以控制细胞生长、线粒体代谢和脂质生物合成。生长因子和细胞能量状态调节 TORC1 的机制已经得到很好的建立,而氨基酸诱导 TORC1 的机制在很大程度上仍然未知。最近的研究表明,Rag GTPases 在调节氨基酸诱导的 TORC1 激活中起着核心作用。在这篇综述中,我们将讨论最近在理解 Rag GTPase 调节 TORC1 激活以响应氨基酸方面的进展。特别关注 Rag GTPases 在 TORC1 激活中的功能以及 Rag GTPases 如何被氨基酸调节。