Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelANF-κB 英文参考文献.docVIP

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Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelANF-κB 英文参考文献.doc

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Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through Cooperation with RelANF-κB 英文参考文献

ForkheadTranscriptionFactorFOXP3UpregulatesCD25 ExpressionthroughCooperationwithRelA/NF-kB CristinaCamperio,SilvanaCaristi,GiorgiaFanelli,MarziaSoligo,PaolaDelPorto,EnzaPiccolella* DepartmentofBiologyandBiotechnology‘‘CharlesDarwin’’,UniversitySapienzaofRome,Rome,Italy Abstract ConsiderableevidencesupportsthepredictionthatCD25isdirectlyregulatedbytheforkheadtranscriptionfactorFOXP3. However,giventhatCD25isnormallyupregulatedinactivatedTcells,regardlessofwhethertheyexpressFOXP3,thisissue + hasstilltobedefinitivelydemonstrated.HerewedescribethatFOXP3,inducedbyCD28signalsinhumanCD4 CD252 T lymphocytes, synergizes with RelA on a regulatory region of Cd25 promoter to mediate the transcriptional activation of Cd25gene.WefoundthatastrikingfeatureofthisregulatoryregionisthepresenceofakBsiteandoftwotandemcopies ofanon-consensusFOXP3bindingsiteseparatedat59endsby19nucleotidesthatallowFOXP3andRelAbindingtoDNA and their physical interaction. The occupancy of the two FOXP3 binding sites in conjunction with RelA binding site occupancyallowsFOXP3tofunctionasapositiveactivatorofCd25gene.IndeedmutationsofbothFOXP3bindingsites suchasmutationofkBsiteonCd25promoterabolishedFOXP3activatoryfunctions.Moreover,FOXP3mutationDE251,that compromises FOXP3 homotypic interactions, failed to trans activate Cd25 promoter, suggesting that both FOXP3 DNA bindinganddimerizationarerequiredtotransactivateCd25promoter.Thesefindingsidentifyanovelmechanismbywhich RelA and FOXP3 cooperate to mediate transcriptional regulation of target genes and characterize a region on Cd25 promoterwhereFOXP3dimercouldbridgeintramolecularlytwoDNAsitesandtransactivateCd25gene. Citation: Camperio C, Caristi S, Fanelli G, Soligo M, Porto PD, et al. (2012) Forkhead Transcription Factor FOXP3 Upregulates CD25 Expression through CooperationwithRelA/NF-kB.PLoSONE7(10):e48303.doi:10.1371/journal.pone.0048303 Editor:DeryaUnutmaz,NewYorkUniversity,UnitedStatesofAmerica ReceivedAugust1,2012;AcceptedSeptember24,2012;Publi