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Title
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Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappa B inhibition
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Author
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Abstract
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| Glucocorticoids are widely used anti-inflammatory and immunomodulatory agents, of which the action mechanism is mainly based on interference of hormone-activated glucocorticoid receptor (GR) with the activity of transcription factors, such as nuclear factor-kappa B (NF-kappa B). In addition to the well described interaction-based mutual repression mechanism between the GR and NF-kappa B, additional mechanisms are at play, which help to explain the efficacy of glucocorticoid-mediated gene repression. In this respect, we found that glucocorticoids counteract the recruitment of activated Mitogen-and Stress-activated protein Kinase-1 (MSK1) at inflammatory gene promoters resulting in the inhibition of NF-kappa B p65 transactivation and of concurrent histone H3 phosphorylation. Additionally, we observed that activated GR can trigger redistribution of nuclear MSK1 to the cytoplasm through a CRM1-dependent export mechanism, as a result of an interaction between liganded GR and activated MSK1. These findings unveil a novel aspect within the GR-mediated NF-kappa B-targeting anti-inflammatory mechanism. |
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Language
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English
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Source (journal)
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The EMBO journal. - Heidelberg, 1982, currens
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Publication
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Heidelberg
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2008
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ISSN
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0261-4189
[print]
1460-2075
[online]
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DOI
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10.1038/EMBOJ.2008.95
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Volume/pages
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27
:12
(2008)
, p. 1682-1693
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ISI
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000256904800004
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Full text (Publisher's DOI)
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