Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation 英文参考文献.docVIP

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Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation 英文参考文献.doc

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Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation 英文参考文献

Ser276PhosphorylationofNF-kBp65byMSK1Controls SCFExpressioninInflammation LaurentReber1,LindaVermeulen2,GuyHaegeman2,NellyFrossard1* 1EA3771, Inflammation and Environment in Asthma, Universite′ Louis Pasteur-Strasbourg-I, Faculte′ de Pharmacie, Illkirch, France, 2LEGEST, Department of Molecular Biology,GhentUniversity,Ghent,Belgium Abstract Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-kB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-kB p65 Ser276 phosphorylation upon IL-1? treatment, which was inhibited in cells transfectedwithaMSK1kinase-dead(KD)mutantcomparedtotheWTcontrol.Inaddition,weshowbyChIPexperiments thatMSK1aswellasMAPKinhibitionabolishesbindingofp65,ofitscoactivatorCBP,andofMSK1itselftothek Bintronic enhancersiteoftheSCFgene.WeshowthatinteractionbetweenNF-kBandCBPispreventedincellstransfectedbyap65 S276C mutant. Finally, we demonstrate that both transfections of MSK1-KD and MSK1 siRNA - but not the WT MSK1 or controlsiRNA-downregulatetheexpressionofSCFinducedbyIL-1?.Ourstudyprovidesthereforeadirectlinkbetween MSK1-mediated phosphorylation of Ser276 p65 of NF-kB, allowing its binding to the SCF intronic enhancer, and pathophysiologicalSCFexpressionininflammation. Citation:ReberL,VermeulenL,HaegemanG,FrossardN(2009)Ser276PhosphorylationofNF-kBp65byMSK1ControlsSCFExpressioninInflammation.PLoS ONE4(2):e4393.doi:10.1371/journal.pone.0004393 Editor:ToruOuchi,NorthwesternUniversity,UnitedStatesofAmerica ReceivedJuly31,2008;AcceptedDecember9,2008;PublishedFebruary6,2009 Copyright: ? 2009 Reber 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:LRissupportedbyagrantfromtheFrenchResearchMinistry(MENRT).Thefundersh