Biology:SESN2
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Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.[1][2][3]
Function
This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions.[3][4] The Sestrins constitute a family of evolutionarily-conserved stress-inducible proteins that suppress oxidative stress and regulate adenosine monophosphate-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis. Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction and muscle degeneration that resemble accelerated tissue aging.[3][5]
Ligands
The NMDA receptor antagonist ketamine has been found to activate the mammalian target of rapamycin complex 1 (mTORC1) pathway in the medial prefrontal cortex (mPFC) of the brain as an essential downstream mechanism in the mediation of its rapid-acting antidepressant effects.[6] NV-5138 is a ligand and modulator of sestrin2, a leucine amino acid sensor and upstream regulatory pathway of mTORC1, and is under development for the treatment of depression.[6] The drug has been found to directly and selectively activate the mTORC1 pathway, including in the mPFC, and to produce rapid-acting antidepressant effects similar to those of ketamine.[6]
See also
References
- ↑ "PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse". Hum Genet 112 (5–6): 573–80. Apr 2003. doi:10.1007/s00439-003-0917-5. PMID 12607115.
- ↑ "Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability". Oncogene 21 (39): 6017–31. Aug 2002. doi:10.1038/sj.onc.1205877. PMID 12203114.
- ↑ 3.0 3.1 3.2 "Entrez Gene: SESN2 sestrin 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=83667.
- ↑ "Sestrins at the crossroad between stress and aging". Aging 2 (6): 369–74. June 2010. doi:10.18632/aging.100157. PMID 20606249.
- ↑ "Sestrins orchestrate cellular metabolism to attenuate aging". Cell Metab 18 (6): 792–801. Dec 2013. doi:10.1016/j.cmet.2013.08.018. PMID 24055102.
- ↑ 6.0 6.1 6.2 "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res 7: 659. 2018. doi:10.12688/f1000research.14344.1. PMID 29899972.
Further reading
- "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD". Science 304 (5670): 596–600. 2004. doi:10.1126/science.1095569. PMID 15105503. Bibcode: 2004Sci...304..596B.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932.
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. 2001. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
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