Research Division, Joslin Diabetes Center, Department of Genetics, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts
Department of MCDB, University of Colorado at Boulder, and.
Genetics. 2019 Oct;213(2):329-360. doi: 10.1534/genetics.119.302504.
The arget f apamycin (TOR or mTOR) is a serine/threonine kinase that regulates growth, development, and behaviors by modulating protein synthesis, autophagy, and multiple other cellular processes in response to changes in nutrients and other cues. Over recent years, TOR has been studied intensively in mammalian cell culture and genetic systems because of its importance in growth, metabolism, cancer, and aging. Through its advantages for unbiased, and high-throughput, genetic and studies, has made major contributions to our understanding of TOR biology. Genetic analyses in the worm have revealed unexpected aspects of TOR functions and regulation, and have the potential to further expand our understanding of how growth and metabolic regulation influence development. In the aging field, has played a leading role in revealing the promise of TOR inhibition as a strategy for extending life span, and identifying mechanisms that function upstream and downstream of TOR to influence aging. Here, we review the state of the TOR field in , and focus on what we have learned about its functions in development, metabolism, and aging. We discuss knowledge gaps, including the potential pitfalls in translating findings back and forth across organisms, but also describe how TOR is important for biology, and how work has developed paradigms of great importance for the broader TOR field.
雷帕霉素（TOR 或 mTOR）的靶点是一种丝氨酸/苏氨酸激酶，通过调节蛋白质合成、自噬和其他多种细胞过程来响应营养物质和其他信号的变化，从而调节生长、发育和行为。近年来，由于 TOR 在生长、代谢、癌症和衰老中的重要性，TOR 在哺乳动物细胞培养和遗传系统中得到了深入研究。通过其在非偏见和高通量遗传和研究中的优势，为我们理解 TOR 生物学做出了重大贡献。线虫中的遗传分析揭示了 TOR 功能和调节的意外方面，并有可能进一步扩展我们对生长和代谢调节如何影响发育的理解。在衰老领域，已经在揭示 TOR 抑制作为延长寿命的策略的前景方面发挥了主导作用，并确定了影响衰老的 TOR 上游和下游的机制。在这里，我们回顾了线虫中的 TOR 领域的现状，并重点介绍了我们在发育、代谢和衰老方面对 TOR 功能的了解。我们讨论了知识差距，包括在不同生物体之间来回翻译发现的潜在陷阱，但也描述了 TOR 对生物学的重要性，以及线虫工作如何为更广泛的 TOR 领域发展具有重要意义的范例。
