COP9 Signalosome Component JAB1CSN5 Is Necessary for T Cell Signaling through LFA-1 and HIV-1 Replication 英文参考文献.docVIP

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COP9 Signalosome Component JAB1CSN5 Is Necessary for T Cell Signaling through LFA-1 and HIV-1 Replication 英文参考文献.doc

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COP9 Signalosome Component JAB1CSN5 Is Necessary for T Cell Signaling through LFA-1 and HIV-1 Replication 英文参考文献

COP9SignalosomeComponentJAB1/CSN5IsNecessary forTCellSignalingthroughLFA-1andHIV-1Replication ShigemiM.Kinoshita1,2*,PeterO.Krutzik3,GarryP.Nolan3,4 1LaboratoryofImmuneRegulation,OsakaUniversityGraduateSchoolofFrontierBiosciences,Suita,Osaka,Japan,2DepartmentofPathology,AnatomyandCellBiology, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America, 3Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford,California,UnitedStatesofAmerica,4DepartmentofMicrobiologyandImmunology,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStates ofAmerica Abstract TodeterminecriticalhostfactorsinvolvedinHIV-1replication,adominanteffectorgeneticsapproachwasdevelopedto revealsignalingpathwaysonwhichHIV-1dependsforreplication.Alargelibraryofshortpeptideaptamerswasexpressed viaretroviraldeliveryinTcells.PeptidesthatinterferedwithTcellactivation-dependentprocessesthatmightsupportHIV-1 replicationwereidentified.Oneoftheselectedpeptidesalteredsignaling,leadtoadifferenceinTcellactivationstatus,and inhibited HIV-1 replication. The target of the peptide was JAB1/CSN5, a component of the signalosome complex. JAB1 expressionovercametheinhibitionofHIV-1replicationinthepresenceofpeptideandalsopromotedHIV-1replicationin + activatedprimaryCD4 Tcells.ThispeptideblockedphysiologicalreleaseofJAB1fromtheaccessoryTcellsurfaceprotein LFA-1,downstreamAP-1dependentevents,NFATactivation,andHIV-1replication.Thus,geneticselectionforintracellular aptamer inhibitors of host cell processes proximal to signals at the immunological synapse of T cells can define unique mechanismsimportanttoHIV-1replication. Citation: Kinoshita SM, Krutzik PO, Nolan GP (2012) COP9 Signalosome Component JAB1/CSN5 Is Necessary for T Cell Signaling through LFA-1 and HIV-1 Replication.PLoSONE7(7):e41725.doi:10.1371/journal.pone.0041725 Editor:KyleneKehn-Hall,GeorgeMasonUniversity,UnitedStatesofAmerica ReceivedApril26,2012;AcceptedJune25,2012;PublishedJuly24,2012 Co