Fission Yeast 26S Proteasome Mutants Are Multi-Drug Resistant Due to Stabilization of the Pap1 Transcription Factor 英文参考文献.docVIP

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Fission Yeast 26S Proteasome Mutants Are Multi-Drug Resistant Due to Stabilization of the Pap1 Transcription Factor 英文参考文献.doc

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Fission Yeast 26S Proteasome Mutants Are Multi-Drug Resistant Due to Stabilization of the Pap1 Transcription Factor 英文参考文献

FissionYeast26SProteasomeMutantsAreMulti-Drug ResistantDuetoStabilizationofthePap1Transcription Factor MaryPenney1,ItaruSamejima1,CarolineR.Wilkinson2,ChristopherJ.McInerny3,S?sG.Mathiassen5, MairiWallace1,TakashiToda4,RasmusHartmann-Petersen5*,ColinGordon1* 1MedicalResearchCouncil,HumanGeneticsUnit,WesternGeneralHospital,Edinburgh,UnitedKingdom,2CellRegulationGroup,PatersonInstituteforCancerResearch, University of Manchester, Manchester, United Kingdom, 3Division of Molecular and Cellular Biology, School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 4Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln’s Inn Fields Laboratories,London,UnitedKingdom,5DepartmentofBiology,UniversityofCopenhagen,Copenhagen,Denmark Abstract Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementationgroups.Cloningexperimentsrevealedthatmostofthemutantswereinessentialgenesencodingvarious 26Sproteasomesubunits.Wefoundthattheproteasomemutantsaremulti-drugresistantduetostabilizationofthestress- activatedtranscriptionfactorPap1.WeshowthattheubiquitylationandultimatelythedegradationofPap1dependonthe Rhp6/Ubc2E2ubiquitinconjugatingenzymeandtheUbr1E3ubiquitin-proteinligase.Accordingly,mutantslackingRhp6 orUbr1displaydrug-resistantphenotypes. Citation:PenneyM,SamejimaI,WilkinsonCR,McInernyCJ,MathiassenSG,etal.(2012)FissionYeast26SProteasomeMutantsAreMulti-DrugResistantDueto StabilizationofthePap1TranscriptionFactor.PLoSONE7(11):e50796.doi:10.1371/journal.pone.0050796 Editor:DeannaM.Koepp,UniversityofMinnesota,UnitedStatesofAmerica ReceivedSeptember14,2012;AcceptedOctober25,2012;PublishedNovember27,2012 Copyright: ? 2012 Penney etal. This is an open-access article distributed under the terms of the Creat