Genetic and Proteomic Evidence for Roles of Drosophila SUMO in Cell Cycle Control, Ras Signaling, and Early Pattern Formation 英文参考文献.docVIP

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Genetic and Proteomic Evidence for Roles of Drosophila SUMO in Cell Cycle Control, Ras Signaling, and Early Pattern Formation 英文参考文献.doc

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Genetic and Proteomic Evidence for Roles of Drosophila SUMO in Cell Cycle Control, Ras Signaling, and Early Pattern Formation 英文参考文献

GeneticandProteomicEvidenceforRolesofDrosophila SUMOinCellCycleControl,RasSignaling,andEarly PatternFormation MinghuaNie1,YongmingXie1,JosephA.Loo1,2,AlbertJ.Courey1* 1DepartmentofChemistryandBiochemistry,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,2DepartmentofBiologicalChemistry, DavidGeffenSchoolofMedicine,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica Abstract SUMO is a protein modifier that is vital for multicellular development. Here we present the first system-wide analysis, combiningmultipleapproaches,tocorrelatethesumoylatedproteome(SUMO-ome)inamulticellularorganismwiththe developmental roles of SUMO. Using mass-spectrometry-based protein identification, we found over 140 largely novel SUMOconjugatesintheearlyDrosophilaembryo.EnrichedfunctionalgroupsincludeproteinsinvolvedinRassignaling,cell cycle, and pattern formation. In support of the functional significance of these findings, sumo germline clone embryos exhibitedphenotypesindicativeofdefectsinthesesamethreeprocesses.Ourcellcultureandimmunolocalizationstudies furthersubstantiaterolesforSUMOinRassignalingandcellcycleregulation.Forexample,wefoundthatSUMOisrequired forefficientRas-mediatedMAPkinaseactivationupstreamoratthelevelofRasactivation.WefurtherfoundthatSUMOis dynamicallylocalizedduringmitosistothecondensedchromosomes,andlateralsotothemidbody.Polokinase,aSUMO substrate found in our screen, partially colocalizes with SUMO at both sites.These studies show that SUMO coordinates multipleregulatoryprocessesduringoogenesisandearlyembryogenesis.Inaddition,ourdatabaseofsumoylatedproteins providesavaluableresourceforthosestudyingtherolesofSUMOindevelopment. Citation:NieM,XieY,LooJA,CoureyAJ(2009)GeneticandProteomicEvidenceforRolesofDrosophilaSUMOinCellCycleControl,RasSignaling,andEarly PatternFormation.PLoSONE4(6):e5905.doi:10.1371/journal.pone.0005905 Editor:MagnusHolm,GothenburgUniversity,Sweden ReceivedApril7,2009;AcceptedMay17,2009;Publishe