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Nitrogendepedent regulation of Rtg1 and Rtg3 in TOR pathway
Manykeysignalingmoleculesareconservedfromyeasttoman.mTORisaproteinkinaseinvolvedinnutrientandgrowthfactorsignalinginhumansthathasayeasthomologwithasimilarrole,TOR1.Likeitshumancounterpart,yeastTOR1isalsoinhibitedbyrapamycin.SignalingdownstreamoftheTORkinasepathwaysregulatesthenuclearlocalizationofseveraltranscriptionfactorsinresponsetothecarbonandnitrogensourcesinthenutritionalenvironment.YeastcellsactivatethetranscriptionfactorGLN3throughtheTORpathwaytocontroltheuseofnitrogeninresponsetonitrogensensing.TORphosphorylationofGLN3whennitrogenisabundantcausescytoplasmiclocalizationandinactivationofthistranscriptionfactor.Whennitrogenisabundant,URE2alsointeractswithGLN3tokeepitoutofthenucleusandrepressed.TORalsoregulatesGLN3throughregulationofthephosphataseSIT4thatdephosphorylatesGLN3inducingnuclearlocalization.Thepreferrednitrogensourcesforyeastcellsareglutamineandglutamate,whicharederivedfromTCAcycleintermediates.TheuseofureaorammoniaasanitrogensourceisassociatedwithinductionofgenesinvolvedintheTCAcyclebythetranscriptionfactorsRTG1andRTG3.Whenglutamineispresent,itcausesrepressionofRTG1andRTG3byTOR1.ThesetofgenesregulateddownstreamofTORaffectcellgrowthassociatedprocessessuchastranslationandnutrientuse.TheABIlityofTORtoselectivelyregulatedifferentsetsofgenesinresponsetoeithercarbonornitrogensourcesindicatesthatTORcaninteractindependentlywiththesedownstreameffectors. Contributor: REFERENCES:Beck,T.andHall,M.N.TheTORsignallingpathwaycontrolsnuclearlocalizationofnutrient-regulatedtranscriptionfactors.Nature,vol402(6762),1999,689-92.BertramPG,etal.ConvergenceofTOR-nitrogenandSnf1-glucosesignalingpathwaysontoGln3.Mol.Cell.Biol.,vol22(4),2002,1246-52.CardenasME,etal.TheTORsignalingcascaderegulatesgeneexpressioninresponsetonutrients.GenesDev.,vol13(24),1999,3271-79.ChanTF,CarvalhoJ,RilesL,andZhengXF.Achemicalgenomicsapproachtowardunderstandingtheglobalfunctionsofthetargetofrapamycinprotein(TOR).PNAS,vol97(24),November2000,13227-32.KomeiliA,WedamanK,O"SheaE,andPowersT.Mechanismofmetaboliccontrol:TargetofrapamycinsignalinglinksnitrogenqualitytotheactivityoftheRtg1andRtg3transcriptionfactors.J.CellBiol.,vol151(4),November2000,863-78.KulkarniAA,etal.Gln3pnuclearlocalizationandinteractionwithUre2pinSaccharomycescerevisiae.J.Biol.Chem.,vol276(34),2002,32136-44.RaughtB,GingrasA,andSonenburgN.Thetargetofrapamycin(TOR)proteins.PNAS,vol98(13),June2001,7037-44.ShamjiAF,KuruvillaFG,andSchreiberSL.PartitioningthetranscriptionalprograminducedbyrapamycinamongtheeffectorsoftheTorproteins.CurrentBIOLOGy,vol10(24),2000,1574-81.
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