Regulation of mTORC1 by amino acids

被引:605
作者
Bar-Peled, Liron [1 ]
Sabatini, David M. [2 ,3 ,4 ,5 ,6 ]
机构
[1] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA
[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[3] MIT, Dept Biol, Cambridge, MA 02142 USA
[4] Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[5] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA
[6] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA
基金
美国国家卫生研究院;
关键词
amino acid sensing; GATOR complex; Ragulator; Rag GTPases; folliculin; TUMOR-SUPPRESSOR COMPLEX; TUBEROUS SCLEROSIS GENE; TRANSFER-RNA SYNTHETASE; GTP-BINDING PROTEINS; P70; S6; KINASE; RAG GTPASES; CELL-GROWTH; CRYSTAL-STRUCTURE; EGO COMPLEX; 3-KINASE/AKT PATHWAY;
D O I
10.1016/j.tcb.2014.03.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mechanistic target of rapamycin complex I (mTORC1) is a central regulator of cellular and organismal growth, and hyperactivation of this pathway is implicated in the pathogenesis of many human diseases including cancer and diabetes. mTORC1 promotes growth in response to the availability of nutrients, such as amino acids, which drive mTORC1 to the lysosomal surface, its site of activation. How amino acid levels are communicated to mTORC1 is only recently coming to light by the discovery of a lysosome-based signaling system composed of Rags (Ras-related GTPases) and Ragulator v-ATPase, GATOR (GAP activity towards Rags), and folliculin (FLCN) complexes. Increased understanding of this pathway will not only provide insight into growth control but also into the human pathologies triggered by its deregulation.
引用
收藏
页码:400 / 406
页数:7
相关论文
共 50 条
[21]   Regulation of TFEB and V-ATPases by mTORC1 [J].
Pena-Llopis, Samuel ;
Vega-Rubin-de-Celis, Silvia ;
Schwartz, Jacob C. ;
Wolff, Nicholas C. ;
Tran, Tram Anh T. ;
Zou, Lihua ;
Xie, Xian-Jin ;
Corey, David R. ;
Brugarolas, James .
EMBO JOURNAL, 2011, 30 (16) :3242-3258
[22]   Regulation of mTORC1 by Upstream Stimuli [J].
Melick, Chase H. ;
Jewell, Jenna L. .
GENES, 2020, 11 (09) :1-28
[23]   Nutrient sensing of mTORC1 signaling in cancer and aging [J].
Jiang, Cong ;
Tan, Xiao ;
Liu, Ning ;
Yan, Peiqiang ;
Hou, Tao ;
Wei, Wenyi .
SEMINARS IN CANCER BIOLOGY, 2024, 106-107 :1-12
[24]   A New Link in the Chain from Amino Acids to mTORC1 Activation [J].
Proud, Chris G. .
MOLECULAR CELL, 2011, 44 (01) :7-8
[25]   Regulation of mTORC1 by lysosomal calcium and calmodulin [J].
Li, Ruo-Jing ;
Xu, Jing ;
Fu, Chenglai ;
Zhang, Jing ;
Zheng, Yujun George ;
Jia, Hao ;
Liu, Jun O. .
ELIFE, 2016, 5
[26]   Nutrient regulation of mTORC1 and cell growth [J].
Yan, Lijun ;
Mieulet, Virginie ;
Lamb, Richard F. .
CELL CYCLE, 2010, 9 (13) :2473-2474
[27]   Regulation of mTORC1 by PI3K signaling [J].
Dibble, Christian C. ;
Cantley, Lewis C. .
TRENDS IN CELL BIOLOGY, 2015, 25 (09) :545-555
[28]   Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9 [J].
Jung, Jennifer ;
Genau, Heide Marika ;
Behrends, Christian .
MOLECULAR AND CELLULAR BIOLOGY, 2015, 35 (14) :2479-2494
[29]   mTORC1, the maestro of cell metabolism and growth [J].
He, Long ;
Cho, Sungyun ;
Blenis, John .
GENES & DEVELOPMENT, 2025, 39 (1-2) :109-131
[30]   Multistep regulation of TFEB by MTORC1 [J].
Vega-Rubin-de-Celis, Silvia ;
Pena-Llopis, Samuel ;
Konda, Meghan ;
Brugarolas, James .
AUTOPHAGY, 2017, 13 (03) :464-472