0 339

Cited 0 times in

The antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1

DC Field Value Language
dc.contributor.author배수한-
dc.contributor.author이서구-
dc.date.accessioned2018-03-26T16:42:45Z-
dc.date.available2018-03-26T16:42:45Z-
dc.date.issued2015-
dc.identifier.issn0891-5849-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/156740-
dc.description.abstractSestrins 1 to 3 constitute a family of proteins that are induced in mammalian cells in response to environmental stressors. Despite their apparent lack of intrinsic catalytic antioxidant activity, Sestrins protect cells from oxidative stress by lowering intracellular levels of H2O2. Here we review the mechanisms by which various types of cellular stress induce Sestrin gene transcription as well as those underlying the antioxidant function of these proteins. Several transcriptional factors, including p53, HIF-1, FoxO, C/EBP-β, ATF4, Nrf2, and PGC-1α, contribute directly to the transcriptional activation of Sestrin genes in response to various types of stress. The antioxidant function of Sestrins is mediated by two main pathways. In one pathway, Sestrins promote the p62-dependent autophagic degradation of Keap1 and thereby upregulate Nrf2 signaling and the consequent expression of genes for antioxidant enzymes. In the second pathway, Sestrins block mTORC1 activation and thereby attenuate reactive oxygen species accumulation. This inhibition of mTORC1 activity is achieved either via the AMPK-dependent phosphorylation and activation of TSC2 and consequent inhibition of the GTPase Rheb or via inhibition of the GTPase Rag and consequent prevention of the lysosomal localization of mTORC1 triggered by amino acids. Elucidation of how these pathways operate individually or cooperatively under different stress conditions awaits further study.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherElsevier Science-
dc.relation.isPartOfFREE RADICAL BIOLOGY AND MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAntioxidants/metabolism*-
dc.subject.MESHAutophagy/physiology*-
dc.subject.MESHHeat-Shock Proteins/metabolism*-
dc.subject.MESHHumans-
dc.subject.MESHIntracellular Signaling Peptides and Proteins/metabolism*-
dc.subject.MESHMechanistic Target of Rapamycin Complex 1-
dc.subject.MESHMultiprotein Complexes/metabolism*-
dc.subject.MESHNF-E2-Related Factor 2/metabolism*-
dc.subject.MESHOxidative Stress/physiology-
dc.subject.MESHSignal Transduction/physiology-
dc.subject.MESHTOR Serine-Threonine Kinases/metabolism*-
dc.titleThe antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorSue Goo Rhee-
dc.contributor.googleauthorSoo Han Bae-
dc.identifier.doi10.1016/j.freeradbiomed.2015.06.007-
dc.contributor.localIdA01798-
dc.contributor.localIdA02847-
dc.relation.journalcodeJ00906-
dc.identifier.eissn1873-4596-
dc.identifier.pmid26117317-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0891584915002750-
dc.subject.keywordAutophagy-
dc.subject.keywordFree radicals-
dc.subject.keywordKeap1-
dc.subject.keywordNrf2-
dc.subject.keywordSestrin-
dc.subject.keywordmTORC1-
dc.subject.keywordp62-
dc.contributor.alternativeNameBae, Soo Han-
dc.contributor.alternativeNameRhee, Sue Goo-
dc.contributor.affiliatedAuthorBae, Soo Han-
dc.contributor.affiliatedAuthorRhee, Sue Goo-
dc.citation.volume88-
dc.citation.numberPt B-
dc.citation.startPage205-
dc.citation.endPage211-
dc.identifier.bibliographicCitationFREE RADICAL BIOLOGY AND MEDICINE, Vol.88(Pt B) : 205-211, 2015-
dc.identifier.rimsid39870-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.