哺乳动物雷帕霉素靶蛋白 (mTOR) 是一种蛋白激酶，可控制细胞代谢、分解代谢、免疫反应、自噬、存活、增殖和迁移，以维持细胞稳态。 mTOR 信号级联由两个不同的多亚基复合物组成，称为 mTOR 复合物 1/2 (mTORC1/2)。 mTOR 催化多种关键蛋白的磷酸化，如 AKT、蛋白激酶 C、胰岛素生长因子受体 (IGF-1R)、4E 结合蛋白 1 (4E-BP1)、核糖体蛋白 S6 激酶 (S6K)、转录因子 EB (TFEB)、甾醇反应元件结合蛋白 (SREBP)、Lipin-1 和 Unc-51 样自噬激活激酶。 mTOR 信号传导在调节翻译、脂质合成、核苷酸合成、溶酶体生物合成、营养传感和生长因子信号传导中发挥着核心作用。新出现的证据表明，mTOR 及其复合物（mTORC1 和 mTORC2）或上游靶标的突变/扩增/缺失导致 mTOR 通路的组成性激活，导致衰老、神经系统疾病和人类恶性肿瘤。在这里，我们提供了 mTOR 及其复合物的详细结构，以及 mTOR 信号级联的上游调节器和下游效应器在代谢、生物分子的生物发生、免疫反应和自噬中的综合作用。此外，我们总结了长非编码 RNA (lncRNA) 作为 mTOR 信号传导重要调节剂的潜力。重要的是，我们强调了 mTOR 信号在衰老、神经系统疾病、人类癌症、癌症干细胞和耐药性方面的潜力。在此，我们讨论 mTOR 信号传导靶向治疗的进展，提高抗癌功效，造福临床癌症患者。© 2023。四川大学华西医院。

The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases. mTOR signaling plays a central role in regulating translation, lipid synthesis, nucleotide synthesis, biogenesis of lysosomes, nutrient sensing, and growth factor signaling. The emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes (mTORC1 and mTORC2) or upstream targets is responsible for aging, neurological diseases, and human malignancies. Here, we provide the detailed structure of mTOR, its complexes, and the comprehensive role of upstream regulators, as well as downstream effectors of mTOR signaling cascades in the metabolism, biogenesis of biomolecules, immune responses, and autophagy. Additionally, we summarize the potential of long noncoding RNAs (lncRNAs) as an important modulator of mTOR signaling. Importantly, we have highlighted the potential of mTOR signaling in aging, neurological disorders, human cancers, cancer stem cells, and drug resistance. Here, we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics.© 2023. West China Hospital, Sichuan University.