p53 Amino-Terminus Region (1–125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype 英文参考文献.docVIP

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p53 Amino-Terminus Region (1–125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype 英文参考文献.doc

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p53 Amino-Terminus Region (1–125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype 英文参考文献

p53Amino-TerminusRegion(1–125)Stabilizesand RestoresHeatDenaturedp53WildPhenotype AnujKumarSharma,AmjadAli,RajanGogna,AmirKumarSingh,UttamPati* TranscriptionandHumanBiologyLab,SchoolofBiotechnology,JawaharlalNehruUniversity,NewDelhi,India Abstract Background:TheintrinsicallydisorderedN-terdomain(NTD)ofp53encompassesapproximatelyhundredaminoacidsthat containatransactivationdomain(1–73)andaproline-richdomain(64–92)andisresponsiblefortransactivationfunction andapoptosis.Italsopossessesanauto-inhibitoryfunctionasitsremovalresultsinremarkablereductionindissociationof p53fromDNA. Principal Findings/Methodology: In this report, we have discovered that p53-NTD spanning amino acid residues 1–125 (NTD125)interactedwithWTp53andstabilizeditswildtypeconformationunderphysiologicalandelevatedtemperatures, bothinvitroandincellularsystems.NTD125preventedirreversiblethermalaggregationofheatdenaturedp53,enhanced p21-59-DBSbindingandfurtherrestoredDBSbindingactivityofheat-denaturedp53,invitro,inadose-dependentmanner. InvivoELISAandimmunoprecipitationanalysisofNTD125-transfectedcellsrevealedthatNTD125shiftedequilibriumfrom p53mutanttowildtypeunderheatstressconditions.Further,NTD125initiatednucleartranslocationofcytoplasmicp53in transcriptionallyactivestateinordertoactivatep53downstreamgenessuchasp21,Bax,PUMA,NoxaandSUMO. Conclusion/Significance:Here,weshowedthatanovelchaperone-likeactivityresidesinp53-N-terregion.Thisstudymight havesignificanceinunderstandingtheroleofp53-NTDinp53stabilization,conformationalactivationandapoptosisunder heat-stressconditions. Citation: Sharma AK, Ali A, Gogna R, Singh AK, Pati U (2009) p53 Amino-Terminus Region (1–125) Stabilizes and Restores Heat Denatured p53 Wild Phenotype.PLoSONE4(10):e7159.doi:10.1371/journal.pone.0007159 Editor:EdatharaAbraham,UniversityofArkansasforMedicalSciences,UnitedStatesofAmerica ReceivedJune8,2009;AcceptedAugust19,2009;PublishedOctober22,2009 Copyright: ? 2009 Sharma et al. This is an open-access article distributed under t