Regulation of mTORC1 and its impact on gene expression at a glance

被引:527
|
作者
Laplante, Mathieu [1 ]
Sabatini, David M. [2 ,3 ,4 ]
机构
[1] Univ Laval, Fac Med, Ctr Rech Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ G1V 4G5, Canada
[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[3] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA
[4] MIT, Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA
基金
加拿大自然科学与工程研究理事会; 美国国家卫生研究院;
关键词
GENETICALLY HETEROGENEOUS MICE; INDUCED INSULIN-RESISTANCE; DIET-INDUCED OBESITY; EXTENDS LIFE-SPAN; MAMMALIAN TARGET; TUBEROUS SCLEROSIS; RAG GTPASES; AMINO-ACID; COMPLEX; ADIPOCYTE DIFFERENTIATION;
D O I
10.1242/jcs.125773
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. Of the two mTOR complexes, mTORC1 is by far the best characterized. When active, mTORC1 triggers cell growth and proliferation by promoting protein synthesis, lipid biogenesis, and metabolism, and by reducing autophagy. The fact that mTORC1 deregulation is associated with several human diseases, such as type 2 diabetes, cancer, obesity and neurodegeneration, highlights its importance in the maintenance of cellular homeostasis. Over the last years, several groups observed that mTORC1 inhibition, in addition to reducing protein synthesis, deeply affects gene transcription. Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPAR gamma, PPAR alpha, HIF1 alpha, YY1-PGC1 alpha and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.
引用
收藏
页码:1713 / 1719
页数:7
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