Departments of Biochemistry, Medicine and Oncology, Faculty of Medicine, Goodman Cancer Research Centre, McGill University, Montréal, Canada.
FEBS J. 2018 May;285(9):1572-1588. doi: 10.1111/febs.14384. Epub 2018 Jan 31.
Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates almost all functions related to cell growth and metabolism in response to extra- and intracellular stimuli, such as availability of nutrients, the presence of growth factors, or the energy status of the cell. As part of two distinct protein complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth and proliferation by controlling ribosome biogenesis, mRNA translation, carbohydrate and lipid metabolism, protein degradation, autophagy as well as microtubule and actin dynamics. In addition to these well-characterized functions, mTOR can also influence gene transcription. While most studies focused on investigating how canonical mTOR signaling regulates the activity of transcription factors outside the nucleus, recent findings point to a more direct role for mTOR as a transcription factor operating on chromatin in the nucleus. In particular, recent genome-wide identification of mTOR targets on chromatin reveals that its activities in the nucleus and cytoplasm are functionally and biologically linked, thus uncovering a novel paradigm in mTOR function.
机械（或哺乳动物）雷帕霉素靶蛋白（mTOR）是一种激酶，可响应细胞外和细胞内刺激（如营养物质的可用性、生长因子的存在或细胞的能量状态）调节与细胞生长和代谢相关的几乎所有功能。作为两个不同的蛋白复合物 mTORC1 和 mTORC2 的一部分，该激酶通过控制核糖体生物发生、mRNA 翻译、碳水化合物和脂质代谢、蛋白质降解、自噬以及微管和肌动蛋白动力学来影响细胞生长和增殖。除了这些特征明确的功能外，mTOR 还可以影响基因转录。虽然大多数研究都集中在研究经典 mTOR 信号如何调节核外转录因子的活性，但最近的发现表明，mTOR 作为一种在核内染色质上起作用的转录因子具有更直接的作用。特别是，最近在染色质上对 mTOR 靶标的全基因组鉴定表明，其在核内和细胞质中的活性在功能和生物学上是相关的，从而揭示了 mTOR 功能的一个新范例。
