Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, SPH2-117, Boston, MA 02115, USA.
Biochem Soc Trans. 2013 Aug;41(4):906-12. doi: 10.1042/BST20130041.
mTOR [mammalian (or mechanistic) target of rapamycin] is a protein kinase that, as part of mTORC1 (mTOR complex 1), acts as a critical molecular link between growth signals and the processes underlying cell growth. Although there has been intense interest in the upstream mechanisms regulating mTORC1, the full repertoire of downstream molecular events through which mTORC1 signalling promotes cell growth is only recently coming to light. It is now recognized that mTORC1 promotes cell growth and proliferation in large part through the activation of key anabolic processes. Through a variety of downstream targets, mTORC1 alters cellular metabolism to drive the biosynthesis of building blocks and macromolecules fundamentally essential for cell growth, including proteins, lipids and nucleic acids. In the present review, we focus on the metabolic functions of mTORC1 as they relate to the control of cell growth and proliferation. As mTORC1 is aberrantly activated in a number of tumour syndromes and up to 80% of human cancers, we also discuss the importance of this mTORC1-driven biosynthetic programme in tumour growth and progression.
mTOR(哺乳动物雷帕霉素靶蛋白)是一种蛋白激酶,作为 mTORC1(mTOR 复合物 1)的一部分,它作为生长信号和细胞生长所必需的过程之间的关键分子联系。尽管人们对调节 mTORC1 的上游机制非常感兴趣,但 mTORC1 信号促进细胞生长的下游分子事件的全部范围最近才开始显现。现在人们认识到,mTORC1 主要通过激活关键的合成代谢过程来促进细胞生长和增殖。通过多种下游靶点,mTORC1 改变细胞代谢,驱动构建块和大分子的生物合成,这些物质对于细胞生长至关重要,包括蛋白质、脂质和核酸。在本综述中,我们重点介绍 mTORC1 的代谢功能,因为它们与细胞生长和增殖的控制有关。由于 mTORC1 在多种肿瘤综合征中异常激活,高达 80%的人类癌症也是如此,我们还讨论了这种 mTORC1 驱动的合成代谢程序在肿瘤生长和进展中的重要性。