Positive Reciprocal Regulation of Ubiquitin C-Terminal Hydrolase L1 and β-CateninTCF Signaling 英文参考文献.docVIP

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Positive Reciprocal Regulation of Ubiquitin C-Terminal Hydrolase L1 and β-CateninTCF Signaling 英文参考文献.doc

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Positive Reciprocal Regulation of Ubiquitin C-Terminal Hydrolase L1 and β-CateninTCF Signaling 英文参考文献

PositiveReciprocalRegulationofUbiquitinC-Terminal HydrolaseL1andb-Catenin/TCFSignaling AnjaliBheda1,WeiYue1,AnuradhaGullapalli1,ChrisWhitehurst1,RenshuiLiu1,JosephS.Pagano1,2, JuliaShackelford1,3 * 1LinebergerComprehensiveCancerCenter,UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,2DepartmentsofMedicine and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3Department of Cell and DevelopmentalBiology,UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica Abstract Deubiquitinatingenzymes(DUBs)areinvolvedintheregulationofdistinctcriticalcellularprocesses.UbiquitinC-terminal Hydrolase L1 (UCH L1) has been linked to several neurological diseases as well as human cancer, but the physiological targetsandtheregulationofUCHL1expressioninvivohavebeenlargelyunexplored.HerewedemonstratethatUCHL1 up-regulatesb-catenin/TCFsignaling:UCHL1formsendogenouscomplexeswithb-catenin,stabilizesitandup-regulatesb- catenin/TCF-dependenttranscription.Wealsoshowthat,reciprocally, b-catenin/TCFsignalingup-regulatesexpressionof endogenousUCHL1mRNAandprotein.Moreover,usingChIPassayanddirectmutagenesisweidentifytwoTCF4-binding sitesontheuchl1promoterthatareinvolvedinthisregulation.SincetheexpressionanddeubiquitinatingactivityofUCH L1arerequiredforitsownbasicpromoteractivity,weproposethatUCHL1up-regulatesitsexpressionbyactivationofthe oncogenicb-catenin/TCFsignalingintransformedcells. Citation:BhedaA,YueW,GullapalliA,WhitehurstC,LiuR,etal.(2009)PositiveReciprocalRegulationofUbiquitinC-TerminalHydrolaseL1andb-Catenin/TCF Signaling.PLoSONE4(6):e5955.doi:10.1371/journal.pone.0005955 Editor:MikhailV.Blagosklonny,RoswellParkCancerInstitute,UnitedStatesofAmerica ReceivedFebruary2,2009;AcceptedMay8,2009;PublishedJune18,2009 Copyright: ? 2009 Bheda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License