SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR 英文参考文献.docVIP
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SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR 英文参考文献
SCS3andYFT2LinkTranscriptionofPhospholipid
BiosyntheticGenestoERStressandtheUPR
RobynD.Moir1,DavidA.Gross1,2,DavidL.Silver1,2*,IanM.Willis1,3
*
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, United States of America, 2Signature Research Program in Cardiovascular and
MetabolicDisorders,Duke–NUSGraduateMedicalSchoolSingapore,Singapore,Singapore,3DepartmentofSystemsandComputationalBiology,AlbertEinsteinCollege
ofMedicine,Bronx,NewYork,UnitedStatesofAmerica
Abstract
Theability tostorenutrients inlipiddroplets(LDs) is anancientfunctionthatprovides theprimarysourceofmetabolic
energyduringperiodsofnutrientinsufficiencyandbetweenmeals.TheFatstorage-InducingTransmembrane(FIT)proteins
are conserved ER–resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the
ancientorthologoftheFITgenefamilyfirstidentifiedinmammalshastwohomologsinSaccharomycescerevisiae(SCS3and
YFT2)andotherfungioftheSaccharomycotinalineage.Despitethecoevolutionofthesegenesformorethan170million
yearsandtheirdivergencefromhighereukaryotes,SCS3,YFT2,andthehumanFIT2generetainsomecommonfunctions:
expressionoftheyeastgenesinahumanembryonickidneycelllinepromotesLDformation,andexpressionofhumanFIT2
inyeastrescuestheinositolauxotrophyandchemicalandgeneticphenotypesofstrainslackingSCS3.Tobetterunderstand
thefunctionofSCS3andYFT2,weinvestigatedthechemicalsensitivitiesofstrainsdeletedforeitherorbothgenesand
identifiedsyntheticgeneticinteractionsagainsttheviableyeastgene-deletioncollection.WeshowthatSCS3andYFT2have
shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid
metabolism,vesiculartrafficking,transcriptionofphospholipidbiosyntheticgenes,andproteinsynthesis.Thegeneticdata
indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that
deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates the
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