Specific SKN-1Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity 英文参考文献.docVIP
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Specific SKN-1Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity 英文参考文献
SpecificSKN-1/NrfStressResponsestoPerturbationsin
TranslationElongationandProteasomeActivity
XuanLi1,2,3,OlliMatilainen4,CongyuJin4,KiraM.Glover-Cutter1,2,CarinaI.Holmberg4*,T.Keith
Blackwell1,2
*
1JoslinDiabetesCenter,HarvardStemCellInstitute,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica,2DepartmentofGenetics,HarvardMedical
School, Boston, Massachusetts, United States of America, 3College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China,
4ResearchProgramsUnit,MolecularCancerBiology,andInstituteofBiomedicine,BiomedicumHelsinki,UniversityofHelsinki,Helsinki,Finland
Abstract
SKN-1, the Caenorhabditis elegans Nrf1/2/3 ortholog, promotes both oxidative stress resistance and longevity. SKN-1
responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive
molecules,aSKN-1/Nrffunctionthatisbothwell-knownandconserved.HereweshowthatSKN-1hasabroaderandmore
complex role in maintaining cellular stress defenses. SKN-1 sustains expression and activity of the ubiquitin-proteasome
system(UPS)andcoordinatesspecificprotectiveresponsestoperturbationsinproteinsynthesisordegradationthrough
theUPS.Iftranslationinitiationorelongationisimpaired,SKN-1upregulatesoverlappingsetsofcytoprotectivegenesand
increasesstressresistance.Whenproteasomegeneexpressionandactivityareblocked,SKN-1activatesmultipleclassesof
proteasomesubunitgenesinacompensatoryresponse.SKN-1therebymaintainsUPSactivityintheintestineinvivounder
normal conditions and promotes survival when the proteasome is inhibited. In contrast, when translation elongation is
impaired,SKN-1doesnotupregulateproteasomegenes,andUPSactivityisthenreduced.ThisindicatesthatUPSactivity
dependsuponpresenceofanintacttranslationelongationapparatus;anditsupportsamodel,suggestedbygeneticand
biochemical studies in yeast, that protein synthesis and degradation may be coupled processes. SKN-1 therefore has a
criticaltissue-specificfunctionininc
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