Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Int J Mol Sci. 2021 Feb 11;22(4):1784. doi: 10.3390/ijms22041784.
The mechanistic target of rapamycin (mTOR) is a master regulator of cell growth, proliferation, and metabolism by integrating various environmental inputs including growth factors, nutrients, and energy, among others. mTOR signaling has been demonstrated to control almost all fundamental cellular processes, such as nucleotide, protein and lipid synthesis, autophagy, and apoptosis. Over the past fifteen years, mapping the network of the mTOR pathway has dramatically advanced our understanding of its upstream and downstream signaling. Dysregulation of the mTOR pathway is frequently associated with a variety of human diseases, such as cancers, metabolic diseases, and cardiovascular and neurodegenerative disorders. Besides genetic alterations, aberrancies in post-translational modifications (PTMs) of the mTOR components are the major causes of the aberrant mTOR signaling in a number of pathologies. In this review, we summarize current understanding of PTMs-mediated regulation of mTOR signaling, and also update the progress on targeting the mTOR pathway and PTM-related enzymes for treatment of human diseases.
雷帕霉素靶蛋白（mTOR）是细胞生长、增殖和代谢的主要调节因子，通过整合各种环境输入，包括生长因子、营养物质和能量等。mTOR 信号通路已被证明可以控制几乎所有基本的细胞过程，如核苷酸、蛋白质和脂质合成、自噬和细胞凋亡。在过去的十五年中，mTOR 通路网络的绘制极大地促进了我们对其上下游信号通路的理解。mTOR 通路的失调常与多种人类疾病有关，如癌症、代谢疾病、心血管疾病和神经退行性疾病。除了遗传改变外，mTOR 成分的翻译后修饰（PTMs）异常也是许多病理中 mTOR 信号异常的主要原因。在这篇综述中，我们总结了目前对 PTMs 介导的 mTOR 信号通路调节的认识，并更新了靶向 mTOR 通路和 PTM 相关酶治疗人类疾病的进展。
