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Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances
Animal Nutrition ( IF 6.3 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.aninu.2021.05.003
Shizhe Zhang 1 , Xueyan Lin 1 , Qiuling Hou 1 , Zhiyong Hu 1 , Yun Wang 1 , Zhonghua Wang 1
Affiliation  

The mechanistic target of rapamycin complex 1 (mTORC1) integrates various types of signal inputs, such as energy, growth factors, and amino acids to regulate cell growth and proliferation mainly through the 2 direct downstream targets, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1). Most of the signal arms upstream of mTORC1 including energy status, stress signals, and growth factors converge on the tuberous sclerosis complex (TSC) − Ras homologue enriched in brain (Rheb) axis. Amino acids, however, are distinct from other signals and modulate mTORC1 using a unique pathway. In recent years, the transmission mechanism of amino acid signals upstream of mTORC1 has been gradually elucidated, and some sensors or signal transmission pathways for individual amino acids have also been discovered. With the help of these findings, we propose a general picture of recent advances, which demonstrates that various amino acids from lysosomes, cytoplasm, and Golgi are sensed by their respective sensors. These signals converge on mTORC1 and form a huge and complicated signal network with multiple synergies, antagonisms, and feedback mechanisms.



中文翻译:

哺乳动物细胞中氨基酸对 mTORC1 的调节:近期进展的总体情况

雷帕霉素复合物 1 (mTORC1) 的机制靶标整合了各种类型的信号输入,如能量、生长因子和氨基酸,主要通过 2 个直接下游靶标来调节细胞生长和增殖,真核翻译起始因子 4E 结合蛋白 1 (4EBP1) 和核糖体蛋白 S6 激酶 1 (S6K1)。mTORC1 上游的大多数信号臂,包括能量状态、压力信号和生长因子,都集中在结节性硬化症 (TSC) - 富含大脑 (Rheb) 轴的 Ras 同系物上。然而,氨基酸与其他信号不同,并使用独特的途径调节 mTORC1。近年来,mTORC1上游氨基酸信号的传递机制逐渐阐明,并且还发现了个别氨基酸的一些传感器或信号传递途径。在这些发现的帮助下,我们提出了最近进展的总体情况,这表明来自溶酶体、细胞质和高尔基体的各种氨基酸被它们各自的传感器感知。这些信号汇聚在 mTORC1 上,形成具有多重协同、拮抗和反馈机制的庞大而复杂的信号网络。

更新日期:2021-10-20
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