Aramburu Jose, Ortells M Carmen, Tejedor Sonia, Buxadé Maria, López-Rodríguez Cristina
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain.
Centre for Genomic Regulation and Universitat Pompeu Fabra, Barcelona 08003, Spain.
Sci Signal. 2014 Jul 1;7(332):re2. doi: 10.1126/scisignal.2005326.
The kinase mammalian target of rapamycin (mTOR) is a central regulator of cell growth and proliferation that integrates inputs from growth factor receptors, nutrient availability, intracellular ATP (adenosine 5'-triphosphate), and a variety of stressors. Since early works in the mid-1990s uncovered the role of mTOR in stimulating protein translation, this kinase has emerged as a rather multifaceted regulator of numerous processes. Whereas mTOR is generally activated by growth- and proliferation-stimulating signals, its activity can be reduced and even suppressed when cells are exposed to a variety of stress conditions. However, cells can also adapt to stress while maintaining their growth capacity and mTOR function. Despite knowledge accumulated on how stress represses mTOR, less is known about mTOR influencing stress responses. In this review, we discuss the capability of mTOR, in particular mTOR complex 1 (mTORC1), to activate stress-responsive transcription factors, and we outline open questions for future investigation.
雷帕霉素哺乳动物靶标(mTOR)激酶是细胞生长和增殖的核心调节因子,它整合来自生长因子受体、营养物质可用性、细胞内三磷酸腺苷(ATP)以及多种应激源的信号输入。自20世纪90年代中期的早期研究揭示mTOR在刺激蛋白质翻译中的作用以来,这种激酶已成为众多过程的一个相当多面的调节因子。虽然mTOR通常由刺激生长和增殖的信号激活,但当细胞暴露于各种应激条件时,其活性会降低甚至被抑制。然而,细胞也可以在维持其生长能力和mTOR功能的同时适应应激。尽管在应激如何抑制mTOR方面已经积累了很多知识,但关于mTOR如何影响应激反应的了解却较少。在这篇综述中,我们讨论了mTOR,特别是mTOR复合物1(mTORC1)激活应激反应转录因子的能力,并概述了未来研究的开放性问题。