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Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation

Laurent Reber, Linda Vermeulen UGent, Guy Haegeman UGent and Nelly Frossard (2009) PLOS ONE. 4(2).
abstract
Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-kappaB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-kappaB p65 Ser276 phosphorylation upon IL-1beta 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 kappaB intronic enhancer site of the SCF gene. We show that interaction between NF-kappaB 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-kappaB, allowing its binding to the SCF intronic enhancer, and pathophysiological SCF expression in inflammation.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
journal title
PLOS ONE
PLoS One
volume
4
issue
2
article_number
e4393
Web of Science type
Article
Web of Science id
000265483700008
JCR category
BIOLOGY
JCR impact factor
4.351 (2009)
JCR rank
9/73 (2009)
JCR quartile
1 (2009)
ISSN
1932-6203
DOI
10.1371/journal.pone.0004393
language
English
UGent publication?
yes
classification
A1
additional info
PMID: 19197368 [PubMed - indexed for MEDLINE] PMCID: PMC2632887
copyright statement
I have transferred the copyright for this publication to the publisher
id
677147
handle
http://hdl.handle.net/1854/LU-677147
date created
2009-06-04 10:01:52
date last changed
2011-11-25 13:31:45
@article{677147,
  abstract     = {Transcription of the mast cell growth factor SCF (stem cell factor) is upregulated in inflammatory conditions, and this is dependent upon NF-kappaB, as well as the MAP kinases p38 and ERK activation. We show here that the MAPK downstream nuclear kinase MSK1 induces NF-kappaB p65 Ser276 phosphorylation upon IL-1beta 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 kappaB intronic enhancer site of the SCF gene. We show that interaction between NF-kappaB 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-kappaB, allowing its binding to the SCF intronic enhancer, and pathophysiological SCF expression in inflammation.},
  articleno    = {e4393},
  author       = {Reber, Laurent and Vermeulen, Linda and Haegeman, Guy and Frossard, Nelly},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  language     = {eng},
  number       = {2},
  title        = {Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation},
  url          = {http://dx.doi.org/10.1371/journal.pone.0004393},
  volume       = {4},
  year         = {2009},
}

Chicago
Reber, Laurent, Linda Vermeulen, Guy Haegeman, and Nelly Frossard. 2009. “Ser276 Phosphorylation of NF-kB P65 by MSK1 Controls SCF Expression in Inflammation.” Plos One 4 (2).
APA
Reber, L., Vermeulen, L., Haegeman, G., & Frossard, N. (2009). Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation. PLOS ONE, 4(2).
Vancouver
1.
Reber L, Vermeulen L, Haegeman G, Frossard N. Ser276 phosphorylation of NF-kB p65 by MSK1 controls SCF expression in inflammation. PLOS ONE. 2009;4(2).
MLA
Reber, Laurent, Linda Vermeulen, Guy Haegeman, et al. “Ser276 Phosphorylation of NF-kB P65 by MSK1 Controls SCF Expression in Inflammation.” PLOS ONE 4.2 (2009): n. pag. Print.