Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway 英文参考文献.docVIP
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Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway 英文参考文献
AktandSHIPModulateFrancisellaEscapefromthe
PhagosomeandInductionoftheFas-MediatedDeath
Pathway
MurugesanV.S.Rajaram1,JonathanP.Butchar1,KishoreV.L.Parsa2,ThomasJ.Cremer3,AmalAmer1,4,
LarryS.Schlesinger1,4,SusheelaTridandapani1,2,3,4
*
1Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America, 2The Ohio State Biochemistry Program, The Ohio State
University, Columbus, Ohio, United States of America, 3Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, Ohio, United
StatesofAmerica,4CenterforMicrobialInterfaceBiology,TheOhioStateUniversity,Columbus,Ohio,UnitedStatesofAmerica
Abstract
Francisellatularensisinfectsmacrophagesandescapesphago-lysosomalfusiontoreplicatewithinthehostcytosol,resulting
inhostcellapoptosis.HereweshowthattheFas-mediateddeathpathwayisactivatedininfectedcellsandcorrelateswith
escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive
activationofAkt,ordeletionofSHIP,promotesphago-lysosomalfusionandlimitsbacterialburdeninthehostcytosol,and
thesubsequentinductionofFasexpressionandcelldeath.Finally,weshowthatphagosomalescape/intracellularbacterial
burdenregulateactivationofthetranscriptionfactorssp1/sp3,leadingtoFasexpressionandcelldeath.Thesedataidentify
forthefirsttimehostcellsignalingpathwaysthatregulatethephagosomalescapeofFrancisella,leadingtotheinductionof
Fasandsubsequenthostcelldeath.
Citation:RajaramMVS,ButcharJP,ParsaKVL,CremerTJ,AmerA,etal.(2009)AktandSHIPModulateFrancisellaEscapefromthePhagosomeandInductionof
theFas-MediatedDeathPathway.PLoSONE4(11):e7919.doi:10.1371/journal.pone.0007919
Editor:ChristopherE.Rudd,UniversityofCambridge,UnitedKingdom
ReceivedJuly1,2009;AcceptedOctober27,2009;PublishedNovember20,2009
Copyright: ? 2009 Rajaram et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricteduse,distribution,andreprod
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