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Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation

Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-κB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-κB p65 Ser276 phosphorylation upon...

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Detalles Bibliográficos
Autores principales: Reber, Laurent, Vermeulen, Linda, Haegeman, Guy, Frossard, Nelly
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632887/
https://www.ncbi.nlm.nih.gov/pubmed/19197368
http://dx.doi.org/10.1371/journal.pone.0004393
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author Reber, Laurent
Vermeulen, Linda
Haegeman, Guy
Frossard, Nelly
author_facet Reber, Laurent
Vermeulen, Linda
Haegeman, Guy
Frossard, Nelly
author_sort Reber, Laurent
collection PubMed
description Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-κB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-κB p65 Ser276 phosphorylation upon IL-1ß treatment, which was inhibited in cells transfected with a MSK1 kinase-dead (KD) mutant compared to the WT control. In addition, we show by ChIP experiments that MSK1 as well as MAPK inhibition abolishes binding of p65, of its coactivator CBP, and of MSK1 itself to the κB intronic enhancer site of the SCF gene. We show that interaction between NF-κB and CBP is prevented in cells transfected by a p65 S276C mutant. Finally, we demonstrate that both transfections of MSK1-KD and MSK1 siRNA - but not the WT MSK1 or control siRNA - downregulate the expression of SCF induced by IL-1ß. Our study provides therefore a direct link between MSK1-mediated phosphorylation of Ser276 p65 of NF-κB, allowing its binding to the SCF intronic enhancer, and pathophysiological SCF expression in inflammation.
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spelling pubmed-26328872009-02-06 Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation Reber, Laurent Vermeulen, Linda Haegeman, Guy Frossard, Nelly PLoS One Research Article Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-κB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-κB p65 Ser276 phosphorylation upon IL-1ß treatment, which was inhibited in cells transfected with a MSK1 kinase-dead (KD) mutant compared to the WT control. In addition, we show by ChIP experiments that MSK1 as well as MAPK inhibition abolishes binding of p65, of its coactivator CBP, and of MSK1 itself to the κB intronic enhancer site of the SCF gene. We show that interaction between NF-κB and CBP is prevented in cells transfected by a p65 S276C mutant. Finally, we demonstrate that both transfections of MSK1-KD and MSK1 siRNA - but not the WT MSK1 or control siRNA - downregulate the expression of SCF induced by IL-1ß. Our study provides therefore a direct link between MSK1-mediated phosphorylation of Ser276 p65 of NF-κB, allowing its binding to the SCF intronic enhancer, and pathophysiological SCF expression in inflammation. Public Library of Science 2009-02-06 /pmc/articles/PMC2632887/ /pubmed/19197368 http://dx.doi.org/10.1371/journal.pone.0004393 Text en Reber et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reber, Laurent
Vermeulen, Linda
Haegeman, Guy
Frossard, Nelly
Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title_full Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title_fullStr Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title_full_unstemmed Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title_short Ser276 Phosphorylation of NF-kB p65 by MSK1 Controls SCF Expression in Inflammation
title_sort ser276 phosphorylation of nf-kb p65 by msk1 controls scf expression in inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632887/
https://www.ncbi.nlm.nih.gov/pubmed/19197368
http://dx.doi.org/10.1371/journal.pone.0004393
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