Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity 英文参考文献.docVIP

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Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity 英文参考文献.doc

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Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity 英文参考文献

Aurora-AInteractswithAP-2aandDownRegulatesIts TranscriptionActivity LihuiZou1,YiminSun2,MingrongWang1,QiminZhan1* 1StateKeyLaboratoryofMolecularOncology,CancerInstituteandCancerHospital,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,Beijing, China,2CapitalBioCorporation,Beijing,China Abstract Aurora-Aisaserine/threonineproteinkinaseandplaysanimportantroleinthecontrolofmitoticprogression.Dysregulated expressionofAurora-Aimpairscentrosomeseparationandmaturation,whichleadtodisruptedcellcycleprogressionand tumorigenesis.However,themolecularmechanismbywhichAurora-Acausescellmalignanttransformationremainstobe further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpressionofAurora-AsuppressedtranscriptionactivityofAP-2a,atumorsuppressorthatisoftendownregulatedin variety oftumors, andinhibited expressionof AP-2a-regulated downstream genes. Thesearray-basedobservations were furtherconfirmedbymicrowellcolorimetricTFassayandluciferasereporterassay.Downregulatedtranscriptionactivityof AP-2abyAurora-AwasfoundtobeassociatedwithreducedAP-2aproteinstability,whichappearedtobemediatedby Aurora-Aenhancedubiquitin-dependentproteasomaldegradationofAP-2aprotein.Interestingly,Aurora-A-mediatedAP- 2adegradationwaslikelydependentAurora-AkinaseactivitysinceinhibitionofAurora-Akinaseactivitywasabletorescue Aurora-A-induced degradation of AP-2a. Moreover, we defined a physical interaction between Aurora-A and AP-2a , and such interaction mightbridge the suppressive effect of Aurora-A on AP-2a protein stability. These findings provide new insightsintomolecularmechanismbywhichAurora-Aactsasanoncogenicmoleculeintumoroccurrenceandmalignant development. Citation:ZouL,SunY,WangM,ZhanQ(2011)Aurora-AInteractswithAP-2aandDownRegulatesItsTranscriptionActivity.PLoSONE6(8):e23110.doi:10.1371/ journal.pone.0023110 Editor:ElianaSaulFurquimWerneckAbdelhay,InstitutoNacionaldeCa?ncer, Brazil ReceivedMay20,2011;AcceptedJuly