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TOR 抑制剂:从哺乳动物结果到植物和藻类中的药物遗传学。

TOR inhibitors: from mammalian outcomes to pharmacogenetics in plants and algae.

机构信息

Aix Marseille Université, CEA, CNRS, BIAM, Laboratoire de génétique et biophysique des plantes, Marseille, F-13009, France.

出版信息

J Exp Bot. 2019 Apr 15;70(8):2297-2312. doi: 10.1093/jxb/erz053.

DOI:10.1093/jxb/erz053
PMID:30773593
Abstract

Target of rapamycin (TOR) is a conserved eukaryotic phosphatidylinositol 3-kinase-related kinase that regulates growth and metabolism in response to environment in plants and algae. The study of the plant and algal TOR pathway has largely depended on TOR inhibitors first developed for non-photosynthetic eukaryotes. In animals and yeast, fundamental work on the TOR pathway has benefited from the allosteric TOR inhibitor rapamycin and more recently from ATP-competitive TOR inhibitors (asTORis) that circumvent the limitations of rapamycin. The asTORis, developed for medical application, inhibit TOR complex 1 (TORC1) more efficiently than rapamycin and also inhibit rapamycin-resistant TORCs. This review presents knowledge on TOR inhibitors from the mammalian field and underlines important considerations for plant and algal biologists. It discusses the use of rapamycin and asTORis in plants and algae and concludes with guidelines for physiological studies and genetic screens with TOR inhibitors.

摘要

雷帕霉素靶蛋白(TOR)是一种保守的真核磷酰肌醇 3-激酶相关激酶,它可以在植物和藻类中响应环境调节生长和代谢。植物和藻类 TOR 通路的研究在很大程度上依赖于最初为非光合真核生物开发的 TOR 抑制剂。在动物和酵母中,TOR 通路的基础工作得益于别构 TOR 抑制剂雷帕霉素,以及最近开发的 ATP 竞争性 TOR 抑制剂(asTORi),这些抑制剂规避了雷帕霉素的局限性。为医学应用而开发的 asTORi 比雷帕霉素更有效地抑制 TOR 复合物 1(TORC1),并抑制雷帕霉素抗性 TORC。这篇综述介绍了来自哺乳动物领域的 TOR 抑制剂的知识,并强调了植物和藻类生物学家的重要考虑因素。它讨论了雷帕霉素和 asTORi 在植物和藻类中的应用,并以使用 TOR 抑制剂进行生理研究和遗传筛选的指南作为结论。

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