AP-2 Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes英文文献资料.docVIP

AP-2 Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes英文文献资料.doc

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AP-2 Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes英文文献资料

HindawiPublishingCorporation JournalofOncology Volume2009,ArticleID780874,9pages doi:10.1155/2009/780874 ResearchArticle AP-2αInhibitsc-MYCInducedOxidativeStressand ApoptosisinHaCaTHumanKeratinocytes LeiYu, 1 MichaelJ.Hitchler, WenqingSun, EhabH.Sarsour, PrabhatC.Goswami, 1 1 1 1 andFrederickE.Domann 1 AloysiusJ.Klingelhutz, 2 1 2 FreeRadicalRadiationBiologyGraduateProgram,RadiationOncologyDepartment,RoyJ.and LucilleA.CarverCollegeofMedicine,TheUniversityofIowa,IowaCity,IA52242,USA DepartmentofMicrobiology,RoyJ.andLucilleA.CarverCollegeofMedicine,TheUniversityofIowa, IowaCity,IA52242,USA CorrespondenceshouldbeaddressedtoFrederickE.Domann,frederick-domann@ Received11June2009;Accepted2October2009 RecommendedbyJ¨orgKlee? AP-2αandc-MYCareimportanttranscriptionfactorsinvolvedinmultiplecellularprocesses.Theyeachdisplaytheparadoxical capacitiestostimulatebothcellproliferationandapoptosisunderdi?erentconditions.Inthepresentstudywefoundthatover expressionofc-MYCwasassociatedwithaccumulationofreactiveoxygenspecies(ROS)andapoptosisinhumankeratinocytes, bothofwhichweresigni?cantlyinhibitedbyco-expressionofAP-2.Thee?ectsofAP-2onc-MYCwereactiveatseverallevels. First,AP-2andc-MYCwerecon?rmedtointeractattheproteinlevelaspreviouslydescribed.Inaddition,forcedexpressionof AP-2signi?cantlydecreasedsteadystatelevelsofc-MYCmRNAandprotein.These?ndingssuggestedthatAP-2mayhaveadirect e?ectonthec-mycgene.ChromatinimmunoprecipitationassaysdemonstratedthatAP-2proteinsboundtoaclusterofAP-2 bindingsiteslocatedwithina2kbupstreamregulatoryregionofc-mycTheseresultssuggestthatthenegativeregulationofAP-2 onc-MYCactivitywasachievedthroughbindingofAP-2proteintothec-mycgene.Thee?ectsofAP-2onc-MYCinducedROS accumulationandapoptosisinepidermalkeratinocytesarelikelytoplayanimportantroleincellgrowth,di?erentiationand carcinogenesisoftheskin. Copyright?2009LeiYuetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which perm

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