A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators 英文参考文献.docVIP

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A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators 英文参考文献.doc

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A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators 英文参考文献

ADivalentIonIsCrucialintheStructureandDominant- NegativeFunctionofIDProteins,aClassofHelix-Loop- HelixTranscriptionRegulators MarieVivianWong1,2.,SizunJiang1.,PaaventhanPalasingam1,PrasannaR.Kolatkar1,2* 1Laboratory for Structural Biochemistry,GenomeInstitute ofSingapore, Singapore,Singapore, 2DepartmentofBiological Sciences, NationalUniversity ofSingapore, Singapore,Singapore Abstract Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcriptionregulators,arewell-characterizedkeyplayersincellularfatedeterminationduringdevelopmentinmammals aswellasDrosophila.Althoughnotoncogenesthemselves,theirupregulationbyvariousoncogenicproteins(suchasRas, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivationoftheubiquitousEproteins,suggestpossiblenovelrolesinengineeringinducedpluripotentstemcells(iPSCs). ? Wepresentthehigh-resolution2.1AcrystalstructureofID2(HLHdomain),coupledwithnovelbiochemicalinsightsinthe presenceofadivalention,possiblycalcium(Ca2+),intheloopofIDproteins,whichappeartobecrucialforthestructure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming. Citation:WongMV,JiangS,PalasingamP,KolatkarPR(2012)ADivalentIonIsCrucialintheStructureandDominant-NegativeFunctionofIDProteins,aClassof Helix-Loop-HelixTranscriptionRegulators.PLoSONE7(10):e48591.doi:10.1371/journal.pone.0048591 Editor:FreddieSalsburyJr,WakeForestUniversity,UnitedStatesofAmerica ReceivedAugust28,2012;AcceptedSeptember28,2012;PublishedOctober30,2012 Copyright: ? 2012 Wong et al. This is an open-access article distributed under the terms of the Crea