硒蛋白作为糖尿病治疗靶点的潜力。
The potential of sestrins as therapeutic targets for diabetes.
作者信息
Dong Xiaocheng Charlie
机构信息
Indiana University School of Medicine, Department of Biochemistry and Molecular Biology , IN 46202 , USA
出版信息
Expert Opin Ther Targets. 2015;19(8):1011-5. doi: 10.1517/14728222.2015.1044976. Epub 2015 May 5.
Abstract
Sestrins (Sesn1/2/3) belong to a small protein family that has versatile biological functions. In addition to initially characterized oxidoreductase activity, sestrins also have oxidoreductase-independent functions, including activation of AMP-activated protein kinase, inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and activation of mTORC2. As these kinases are important for metabolic regulation, sestrins have a favorable profile as potential therapeutic targets for metabolic diseases such as diabetes. Recent data are in line with such a notion. In this editorial, I have attempted to provide a brief update on the major findings in regard to sestrins in metabolism.
摘要
硒蛋白（Sesn1/2/3）属于一个具有多种生物学功能的小蛋白家族。除了最初被描述的氧化还原酶活性外，硒蛋白还具有不依赖氧化还原酶的功能，包括激活AMP激活的蛋白激酶、抑制雷帕霉素复合物1（mTORC1）的机制靶点以及激活mTORC2。由于这些激酶对代谢调节很重要，硒蛋白作为糖尿病等代谢疾病的潜在治疗靶点具有良好的前景。最近的数据支持这一观点。在这篇社论中，我试图简要介绍一下关于硒蛋白在代谢方面的主要研究结果。
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本文引用的文献
1
Insulin Increases Sestrin 2 Content by Reducing Its Degradation through the PI 3 K/mTOR Signaling Pathway.胰岛素通过减少 PI3K/mTOR 信号通路的降解来增加 sestrin 2 的含量。
Int J Endocrinol. 2015;2015:505849. doi: 10.1155/2015/505849. Epub 2015 Feb 22.
2
Sestrins inhibit mTORC1 kinase activation through the GATOR complex.硒蛋白通过GATOR复合体抑制mTORC1激酶的激活。
Cell Rep. 2014 Nov 20;9(4):1281-91. doi: 10.1016/j.celrep.2014.10.019.
3
Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling.硒蛋白3通过直接激活mTORC2-Akt信号通路增强肝脏胰岛素敏感性。
Diabetes. 2015 Apr;64(4):1211-23. doi: 10.2337/db14-0539. Epub 2014 Nov 5.
4
The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1.硒蛋白与GATOR2相互作用，以负向调节mTORC1上游的氨基酸感应通路。
Cell Rep. 2014 Oct 9;9(1):1-8. doi: 10.1016/j.celrep.2014.09.014. Epub 2014 Sep 25.
5
Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling.硒代半胱氨酸作为Rag GTP酶的鸟嘌呤核苷酸解离抑制剂，以控制mTORC1信号传导。
Cell. 2014 Sep 25;159(1):122-133. doi: 10.1016/j.cell.2014.08.038.
6
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FEBS J. 2014 Sep;281(17):3816-27. doi: 10.1111/febs.12905. Epub 2014 Jul 28.
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Am J Physiol Gastrointest Liver Physiol. 2014 Jul 1;307(1):G58-65. doi: 10.1152/ajpgi.00373.2013. Epub 2014 May 15.
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Am J Physiol Endocrinol Metab. 2013 Dec 1;305(11):E1408-14. doi: 10.1152/ajpendo.00212.2013. Epub 2013 Oct 15.
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