Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation 英文参考文献.docVIP

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Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation 英文参考文献.doc

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Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation 英文参考文献

ExtensiveGene-SpecificTranslationalReprogrammingin aModelofBCellDifferentiationandAbl-Dependent Transformation JamieG.Bates1,2,JuliaSalzman1,2,DamonMay3,PattyB.Garcia4,GregoryJ.Hogan1,2,MartinMcIntosh3, MarkS.Schlissel4,PatO.Brown1,2* 1Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America, 2Howard Hughes Medical Institute, Stanford, California,UnitedStatesofAmerica,3ComputationalProteomicsLaboratory,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica, 4DepartmentofMolecularCellBiology,UniversityofCalifornia,Berkeley,California,UnitedStatesofAmerica Abstract Towhatextentmighttheregulationoftranslationcontributetodifferentiationprograms,ortothemolecularpathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimicsleukemiaswithaBCR-ABL1translocation,suchasChronicMyelogenousLeukemia(CML)andAcuteLymphoblastic Leukemia(ALL).InhibitionoftheoncogenicAblkinasewithimatinibreversestransformation,allowingprogressiontothe next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigatetheextentandpotentialcontributionoftranslationalregulationtotransformationanddifferentiationinv-Abl- transformedpre-Bcells.Overhalfofthesignificantlytranslationallyregulatedgenesdidnotchangesignificantlyatthelevel ofmRNAabundance,revealingbiologythatmighthavebeenmissedbymeasuringchangesintranscriptabundancealone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiationandmalignanttransformation. Citation:BatesJG,SalzmanJ,MayD,GarciaPB,HoganGJ,etal.(2012)ExtensiveGene-SpecificTrans