Nucleolar Proteins Suppress Caenorhabditis elegans Innate Immunity by Inhibiting p53CEP-1 英文参考文献.docVIP

Nucleolar Proteins Suppress Caenorhabditis elegans Innate Immunity by Inhibiting p53CEP-1 英文参考文献.doc

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Nucleolar Proteins Suppress Caenorhabditis elegans Innate Immunity by Inhibiting p53CEP-1 英文参考文献

NucleolarProteinsSuppressCaenorhabditiselegansInnate ImmunitybyInhibitingp53/CEP-1 LauraE.Fuhrman1,AjayKumarGoel1,JasonSmith2,KevinV.Shianna2,AlejandroAballay1* 1DepartmentofMolecularGeneticsandMicrobiology,DukeUniversityMedicalCenter;Durham,NorthCarolina,UnitedStatesofAmerica,2InstituteforGenomeSciences Policy,DukeUniversity,Durham,NorthCarolina,UnitedStatesofAmerica Abstract Thetumorsuppressorp53hasbeenimplicatedinmultiplefunctionsthatplaykeyrolesinhealthanddisease,including ribosomebiogenesis,controlofaging,andcellcycleregulation.Ageneticscreenfornegativeregulatorsofinnateimmunity inCaenorhabditiselegansledtotheidentificationofamutationinNOL-6,anucleolarRNA-associatedprotein(NRAP),which isinvolvedinribosomebiogenesisandconservedacrosseukaryoticorganisms.MutationorsilencingofNOL-6andother nucleolarproteinsresultsinanenhancedresistancetobacterialinfections.Afull-genomemicroarrayanalysisonanimals withalteredimmunefunctionduetomutationinnol-6showsincreasedtranscriptionallevelsofgenesregulatedbyap53 homologue, CEP-1. Further studies indicate that the activation of innate immunity by inhibition of nucleolar proteins requiresp53/CEP-1anditstranscriptionaltargetSYM-1.Sincenucleoliandp53/CEP-1areconserved,ourresultsrevealan ancientimmunemechanismbywhichthenucleolusmayregulateimmuneresponsesagainstbacterialpathogens. Citation:FuhrmanLE,GoelAK,SmithJ,ShiannaKV,AballayA(2009)NucleolarProteinsSuppressCaenorhabditiselegansInnateImmunitybyInhibitingp53/CEP-1.PLoS Genet5(9):e1000657.doi:10.1371/journal.pgen.1000657 Editor:StuartK.Kim,StanfordUniversityMedicalCenter,UnitedStatesofAmerica ReceivedMay15,2009;AcceptedAugust20,2009;PublishedSeptember18,2009 Copyright: ? 2009 Fuhrman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkissupportedbyNIHGM070977.Thefundershadnoroleinstudydesign,da

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