Expression and Functional Studies of Ubiquitin C-Terminal Hydrolase L1 Regulated Genes 英文参考文献.docVIP

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Expression and Functional Studies of Ubiquitin C-Terminal Hydrolase L1 Regulated Genes 英文参考文献.doc

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Expression and Functional Studies of Ubiquitin C-Terminal Hydrolase L1 Regulated Genes 英文参考文献

ExpressionandFunctionalStudiesofUbiquitinC- TerminalHydrolaseL1RegulatedGenes AnjaliBheda1,JuliaShackelford1,3,JosephS.Pagano1,2 * 1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America, 2Departments of Medicine and MicrobiologyImmunology,UniversityofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica,3DepartmentofCellDevelopmentalBiology,University ofNorthCarolina,ChapelHill,NorthCarolina,UnitedStatesofAmerica Abstract Deubiquitinatingenzymes(DUBs)havebeenincreasinglyimplicatedinregulationofcellularprocesses,butafunctionalrole forUbiquitinC-terminalHydrolases(UCHs),whichhasbeenlargelyrelegatedtoprocessingofsmallubiquitinatedpeptides, remainsunexplored.OnememberoftheUCHfamily,UCHL1,isexpressedinanumberofmalignanciessuggestingthatthis DUBmightbeinvolvedinoncogenicprocesses,andincreasedexpressionandactivityofUCHL1havebeendetectedin EBV-immortalized cell lines. Here we present an analysis of genes regulated by UCH L1 shown by microarray profiles obtainedfromcellsinwhichexpressionofthegenewasinhibitedbyRNAi.Microarraydatawereverifiedwithsubsequent real-timePCRanalysis.WefoundthatinhibitionofUCHL1activatesgenesthatcontrolapoptosis,cellcyclearrestandatthe same time suppresses expression of genes involved in proliferation and migration pathways. These findings are complementedbybiologicalassaysforapoptosis,cellcycleprogressionandmigrationthatsupportthedataobtainedfrom microarrayanalysis,andsuggestthatthemulti-functionalmoleculeUCHL1playsaroleinregulatingprincipalpathways involvedinoncogenesis. Citation:BhedaA,ShackelfordJ,PaganoJS(2009)ExpressionandFunctionalStudiesofUbiquitinC-TerminalHydrolaseL1RegulatedGenes.PLoSONE4(8): e6764.doi:10.1371/journal.pone.0006764 Editor:NeerajVij,JohnsHopkinsSchoolofMedicine,UnitedStatesofAmerica ReceivedMay12,2009;AcceptedJuly24,2009;PublishedAugust26,2009 Copyright: ? 2009 Bheda et al. This is an open-access article distributed under the terms of the Creative