View the Current Issue

Article

  • The EMBO Journal (2008) 27, 1682 - 1693
  • doi:10.1038/emboj.2008.95

Published online: 29 May 2008

Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition

Ilse M E Beck1, Wim Vanden Berghe1, Linda Vermeulen1, Nadia Bougarne1, Bert Vander Cruyssen2, Guy Haegeman1,3 and Karolien De Bosscher1,3

  1. Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Molecular Biology, Gent University, Gent, Belgium
  2. Department of Rheumatology, Ghent University Hospital, Gent, Belgium
  3. Both of these authors share senior authorship

Correspondence to:

Guy Haegeman, Department of Molecular Biology, Ghent University, LEGEST, KL Ledeganckstraat 35, Gent B-9000, Belgium. Tel.: +32 9 264 5166; Fax: +32 9 264 5304; E-mail: Guy.Haegeman@ugent.be

Received 18 June 2007; Accepted 15 April 2008

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.

  • Keywords:

    • glucocorticoid,
    • inflammation,
    • MSK1,
    • NF-kappaB,
    • translocation