硒蛋白通过RRAGs调节mTORC1：GATOR之谜。
SESTRINs regulate mTORC1 via RRAGs: The riddle of GATOR.
作者信息
Budanov Andrei V
机构信息
Department of Human and Molecular Genetics; Goodwin Research Laboratories; Massey Cancer Center; Virginia Commonwealth University ; Richmond, VA, USA.
出版信息
Mol Cell Oncol. 2015 Jan 23;2(3):e997113. doi: 10.1080/23723556.2014.997113. eCollection 2015 Jul-Sep.
Abstract
SESTRINs, proteins encoded by the SESN1-3 genes in mammals, are well-established suppressors of the mechanistic target of rapamycin complex 1 (mTORC1) kinase. Recently, we found that SESTRINs bind the GATOR2 protein complex, which is a regulator of RRAGA/B guanosine triphosphatase. Three independent studies support the RRAGA/B-dependence of mTORC1 regulation by SESTRINs; however, the role of GATOR2 in this process requires clarification.
摘要
SESTRINs是哺乳动物中由SESN1 - 3基因编码的蛋白质，是雷帕霉素复合物1（mTORC1）激酶机制靶点的成熟抑制因子。最近，我们发现SESTRINs与GATOR2蛋白复合物结合，GATOR2蛋白复合物是RRAGA/B鸟苷三磷酸酶的调节因子。三项独立研究支持SESTRINs对mTORC1调节的RRAGA/B依赖性；然而，GATOR2在此过程中的作用需要阐明。
相似文献
1
SESTRINs regulate mTORC1 via RRAGs: The riddle of GATOR.硒蛋白通过RRAGs调节mTORC1：GATOR之谜。
Mol Cell Oncol. 2015 Jan 23;2(3):e997113. doi: 10.1080/23723556.2014.997113. eCollection 2015 Jul-Sep.
2
Locked in Structure: Sestrin and GATOR-A Billion-Year Marriage.锁定结构：Ses 蛋白和 GATOR—长达十亿年的婚姻。
Cells. 2024 Sep 21;13(18):1587. doi: 10.3390/cells13181587.
3
p53-inducible SESTRINs might play opposite roles in the regulation of early and late stages of lung carcinogenesis.p53诱导的硒蛋白S可能在肺癌发生的早期和晚期调控中发挥相反作用。
Oncotarget. 2019 Dec 10;10(65):6997-7009. doi: 10.18632/oncotarget.27367.
4
Glucose-Induced Activation of mTORC1 is Associated with Hexokinase2 Binding to Sestrins in HEK293T Cells.葡萄糖诱导的 mTORC1 激活与 HEK293T 细胞中己糖激酶 2 与 Sestrins 的结合有关。
J Nutr. 2023 Apr;153(4):988-998. doi: 10.1016/j.tjnut.2022.11.021. Epub 2022 Dec 22.
5
The potential of sestrins as therapeutic targets for diabetes.硒蛋白作为糖尿病治疗靶点的潜力。
Expert Opin Ther Targets. 2015;19(8):1011-5. doi: 10.1517/14728222.2015.1044976. Epub 2015 May 5.
6
Sestrin2 inhibits mTORC1 through modulation of GATOR complexes.硒蛋白2通过调节GATOR复合体来抑制mTORC1。
Sci Rep. 2015 Mar 30;5:9502. doi: 10.1038/srep09502.
7
Sestrins are differentially expressed with age in the skeletal muscle of men: A cross-sectional analysis.成纤维细胞生长因子 21 通过调节自噬促进衰老肌肉卫星细胞的再生
Exp Gerontol. 2018 Sep;110:23-34. doi: 10.1016/j.exger.2018.05.006. Epub 2018 May 8.
8
Role of sestrins in metabolic and aging-related diseases.Sesrins 在代谢和衰老相关疾病中的作用。
Biogerontology. 2024 Feb;25(1):9-22. doi: 10.1007/s10522-023-10053-y. Epub 2023 Jul 30.
9
Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia.GATOR复合体基因在家族性局灶性癫痫和局灶性皮质发育不良中的作用。
Epilepsia. 2016 Jun;57(6):994-1003. doi: 10.1111/epi.13391. Epub 2016 May 13.
10
Sestrins: A New Kid for Stroke Treatment?硒蛋白：中风治疗的新希望？
Curr Drug Deliv. 2017 Sep 6;14(6):797-806. doi: 10.2174/1567201814666161111125249.
引用本文的文献
1
is required for lifespan extension during caloric deprivation in through inhibition of mTORC1 and activation of autophagy.通过抑制mTORC1和激活自噬，在热量限制期间延长寿命是必需的。
Aging (Albany NY). 2025 Jul 28;17(7):1834-1851. doi: 10.18632/aging.206290.
2
Association of plasma levels of Sestrin2 with adiposity and metabolic function indices in healthy and diabetic subjects from Qatar Biobank.卡塔尔生物样本库中健康和糖尿病受试者血浆中Sestrin2水平与肥胖及代谢功能指标的关联
Front Endocrinol (Lausanne). 2025 May 13;16:1518388. doi: 10.3389/fendo.2025.1518388. eCollection 2025.
3
p53-regulated SESN1 and SESN2 regulate cell proliferation and cell death through control of STAT3.p53调控的SESN1和SESN2通过控制STAT3来调节细胞增殖和细胞死亡。
Cell Commun Signal. 2025 Feb 22;23(1):105. doi: 10.1186/s12964-025-02104-3.
4
Locked in Structure: Sestrin and GATOR-A Billion-Year Marriage.锁定结构：Ses 蛋白和 GATOR—长达十亿年的婚姻。
Cells. 2024 Sep 21;13(18):1587. doi: 10.3390/cells13181587.
5
SESN1 attenuates the Ox‑LDL‑induced inflammation, apoptosis and endothelial‑mesenchymal transition of human umbilical vein endothelial cells by regulating AMPK/SIRT1/LOX1 signaling.SESN1 通过调节 AMPK/SIRT1/LOX1 信号通路抑制 Ox-LDL 诱导的人脐静脉内皮细胞炎症、凋亡及内皮-间充质转化。
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12678. Epub 2022 Mar 16.
6
Mitochondrial localization of SESN2. SESN2 的线粒体定位。
PLoS One. 2020 Apr 14;15(4):e0226862. doi: 10.1371/journal.pone.0226862. eCollection 2020.
7
p53-inducible SESTRINs might play opposite roles in the regulation of early and late stages of lung carcinogenesis.p53诱导的硒蛋白S可能在肺癌发生的早期和晚期调控中发挥相反作用。
Oncotarget. 2019 Dec 10;10(65):6997-7009. doi: 10.18632/oncotarget.27367.
8
Potential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge.RagA-mTOR-p70S6K 轴与细菌脂多糖刺激期间抑郁行为之间的潜在联系。
J Neuroinflammation. 2019 Nov 11;16(1):211. doi: 10.1186/s12974-019-1610-5.
9
A coding and non-coding transcriptomic perspective on the genomics of human metabolic disease.从编码和非编码转录组学角度看人类代谢疾病的基因组学。
Nucleic Acids Res. 2018 Sep 6;46(15):7772-7792. doi: 10.1093/nar/gky570.
10
Mitochondrial AKAP1 supports mTOR pathway and tumor growth.线粒体锚定蛋白1支持雷帕霉素靶蛋白（mTOR）信号通路及肿瘤生长。
Cell Death Dis. 2017 Jun 1;8(6):e2842. doi: 10.1038/cddis.2017.241.
本文引用的文献
1
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.
2
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.
3
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.
4
Regulation of mTORC1 by amino acids.氨基酸对mTORC1的调控
Trends Cell Biol. 2014 Jul;24(7):400-6. doi: 10.1016/j.tcb.2014.03.003. Epub 2014 Mar 31.
5
Amino acids activate mammalian target of rapamycin (mTOR) complex 1 without changing Rag GTPase guanyl nucleotide charging.氨基酸在不改变 Rag GTP 酶鸟苷核苷酸充电的情况下激活哺乳动物雷帕霉素靶蛋白（mTOR）复合物 1。
J Biol Chem. 2014 Jan 31;289(5):2658-74. doi: 10.1074/jbc.M113.528505. Epub 2013 Dec 11.
6
SEACing the GAP that nEGOCiates TORC1 activation: evolutionary conservation of Rag GTPase regulation.SEACing 调节 TORC1 激活的 GAP： Rag GTPase 调节的进化保守性。
Cell Cycle. 2013 Sep 15;12(18):2948-52. doi: 10.4161/cc.26000. Epub 2013 Aug 13.
7
mTOR signaling in growth control and disease.mTOR 信号在生长控制和疾病中的作用。
Cell. 2012 Apr 13;149(2):274-93. doi: 10.1016/j.cell.2012.03.017.
8
A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae.在酿酒酵母中，一种包含 Sec13 和 Seh1 的保守的COP 相关复合物与液泡动态相关。
Mol Cell Proteomics. 2011 Jun;10(6):M110.006478. doi: 10.1074/mcp.M110.006478. Epub 2011 Mar 31.
9
Stressin' Sestrins take an aging fight.应激 Sestrin 抵抗衰老。
EMBO Mol Med. 2010 Oct;2(10):388-400. doi: 10.1002/emmm.201000097.
10
p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling.p53靶基因硒蛋白1和硒蛋白2将基因毒性应激与mTOR信号传导联系起来。
Cell. 2008 Aug 8;134(3):451-60. doi: 10.1016/j.cell.2008.06.028.
Zotero 插件