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- Title
Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition.
- Authors
Beck, Ilse M E; Vanden Berghe, Wim; Vermeulen, Linda; Bougarne, Nadia; Vander Cruyssen, Bert; Haegeman, Guy; De Bosscher, Karolien
- Abstract
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-kappaB (NF-kappaB). In addition to the well described interaction-based mutual repression mechanism between the GR and NF-kappaB, 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-kappaB 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-kappaB-targeting anti-inflammatory mechanism.
- Publication
The EMBO journal, 2008, Vol 27, Issue 12, p1682
- ISSN
1460-2075
- Publication type
Journal Article
- DOI
10.1038/emboj.2008.95