Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins 英文参考文献.docVIP

Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins 英文参考文献.doc

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Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins 英文参考文献

ProteomicAnalysisRevealsNewCardiac-Specific Dystrophin-AssociatedProteins EricK.Johnson1,LiwenZhang2,MarvinE.Adams3,AlistairPhillips4,MichaelA.Freitas5, StanleyC.Froehner3,KariB.Green-Church2,FedericaMontanaro1,6* 1CenterforGeneTherapy,TheResearchInstituteatNationwideChildren’sHospital,andtheOhioStateUniversityBiochemistryProgram,Columbus,Ohio,UnitedStates ofAmerica,2CenterforBiomedicalEPRSpectroscopyandImaging,theOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica,3DepartmentofPhysiologyand Biophysics, University of Washington, Seattle, Washington, United States of America, 4Division of Cardiothoracic Surgery, The Heart Institute, Cincinnati Children’s Hospital,Cincinnati,Ohio,UnitedStatesofAmerica,5DepartmentofMolecularVirology,ImmunologyandMedicalGenetics,ComprehensiveCancerCenter,TheOhio StateUniversity,Columbus,Ohio,UnitedStatesofAmerica,6DepartmentofPediatrics,TheOhioStateUniversityCollegeofMedicine,Columbus,Ohio,UnitedStatesof America Abstract Mutationsaffectingtheexpressionofdystrophinresultinprogressivelossofskeletalmusclefunctionandcardiomyopathy leadingtoearlymortality.Interestingly,clinicalstudiesrevealednocorrelationindiseaseseverityorageofonsetbetween cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles.Sincedystrophinservesasastructuralandsignalingscaffold,functionaldifferenceslikelyarisefromtissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac- specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involv

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