A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity 英文参考文献.docVIP

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A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity 英文参考文献.doc

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A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity 英文参考文献

ANewNuclearFunctionoftheEntamoebahistolytica GlycolyticEnzymeEnolase:TheMetabolicRegulationof Cytosine-5Methyltransferase2(Dnmt2)Activity AyalaTovy1,RamaSimanTov1,RicardaGaentzsch2,MarkHelm2,3,SergeAnkri1* 1Department of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel, 2Department of Chemistry, The Pharmacy and Molecular BiotechnologyInstitute,Ruprecht-KarlsUniversityofHeidelberg,Heidelberg,Germany,3ThePharmacyandBiochemistryInstitute,JohannesGutenbergUniversity,Mainz, Germany Abstract Cytosine-5methyltransferasesoftheDnmt2familyfunctionasDNAandtRNAmethyltransferases.Insightintotheroleand biologicalsignificanceofDnmt2isgreatlyhamperedbyalackofknowledgeaboutitsproteininteractions.Inthisreport,we address thesubject ofproteininteractionby identifyingenolasethrougha yeasttwo-hybrid screenasaDnmt2-binding protein.Enolase,whichisknowntocatalyzetheconversionof2-phosphoglycerate(2-PG)tophosphoenolpyruvate(PEP), wasshowntohavebothacytoplasmaticandanuclearlocalizationintheparasiteEntamoebahistolytica.Wediscoveredthat enolaseactsasaDnmt2inhibitor.Thisunexpectedinhibitoryactivitywasantagonizedby2-PG,whichsuggeststhatglucose metabolismcontrolsthenon-glycolyticfunctionofenolase.Interestingly,glucosestarvationdrivesenolasetoaccumulate within the nucleus, which in turn leads to the formation of additional enolase-E.histolytica DNMT2 homolog (Ehmeth) complex,andtoasignificantreductionofthetRNAAspmethylationintheparasite.ThecrucialroleofenolaseasaDnmt2 inhibitorwasalsodemonstratedinE.histolyticaexpressinganuclearlocalizationsignal(NLS)-fused-enolase.Theseresults establish enolase as the first Dnmt2 interacting protein, and highlight an unexpected role of a glycolytic enzyme in the modulationofDnmt2activity. Citation: Tovy A, Siman Tov R, Gaentzsch R, Helm M, Ankri S (2010) A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The MetabolicRegulationofCytosine-5Methyltransferase2(Dnmt2)Activity.PLoSPathog6(2):e1000