Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, Canada.
J Cell Sci. 2013 Apr 15;126(Pt 8):1713-9. doi: 10.1242/jcs.125773. Epub 2013 May 2.
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, PPARγ, PPARα, HIF1α, YY1–PGC1α 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.
雷帕霉素的哺乳动物靶标(mTOR)是一种激酶,可调节与促进细胞生长和代谢有关的关键细胞功能。这种激酶是两种蛋白复合物的一部分,称为 mTOR 复合物 1(mTORC1)和 2(mTORC2),它在协调对生长因子和营养物质的合成代谢和分解代谢过程中起着至关重要的作用。在这两个 mTOR 复合物中,mTORC1 是迄今为止研究最充分的。当处于活跃状态时,mTORC1 通过促进蛋白质合成、脂质生物发生和代谢以及减少自噬来触发细胞生长和增殖。事实上,mTORC1 的失调与几种人类疾病有关,如 2 型糖尿病、癌症、肥胖和神经退行性变,这凸显了它在维持细胞内稳态中的重要性。在过去的几年中,有几个研究小组观察到,mTORC1 的抑制作用除了减少蛋白质合成外,还会深度影响基因转录。在这里,我们通过关注 mTORC1 对包括 STAT3、SREBPs、PPARγ、PPARα、HIF1α、YY1-PGC1α 和 TFEB 在内的特定转录因子的激活的影响,来回顾 mTORC1 与基因转录之间的联系。我们还讨论了这些转录因子在介导 mTORC1 对生理和病理条件下各种细胞过程的影响方面的重要性。