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Mitogen- and stress-activated protein kinase 1 MSK1 regulates glucocorticoid response element promoter activity in a

Ilse M Beck1, Dorien Clarisse, Nadia Bougarne

  • 1Laboratory of Experimental Cancer Research, Department of Radiation Therapy & Experimental Cancer Research, Ghent University, UZ 1P7, De Pintelaan 185, B-9000 Gent, Belgium. Ilse.Beck@UGent.be

European Journal of Pharmacology
|July 9, 2013
PubMed

Insights

Mitogen- and stress-activated protein kinase (MSK1) impacts glucocorticoid receptor (GR) activity. MSK1 or MAPK inhibition affects GR transactivation differently based on GR activation levels, suggesting complex roles in anti-inflammatory therapies.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Pharmacology

Background:

  • The glucocorticoid receptor (GR) is a key regulator of cellular responses, often acting through anti-inflammatory mechanisms.
  • Mitogen- and stress-activated protein kinase 1 (MSK1) is involved in chromatin remodeling and stress responses.
  • GR can target MSK1 for anti-inflammatory effects, but the converse interaction is less understood.

Purpose of the Study:

  • To investigate the impact of MSK1 and its upstream kinases on GR-mediated transactivation.
  • To explore the concentration-dependent effects of MSK1 and MAPK inhibition on GR activity.
  • To elucidate the role of MSK1 in GR's nucleocytoplasmic translocation.

Main Methods:

  • Utilized reporter gene assays to measure GRE-regulated promoter activity.
  • Employed kinase inhibitors (H89, SB203580, U0126) to modulate MSK1 and MAPK activity.
  • Assessed glucocorticoid-induced nucleocytoplasmic translocation of MSK1.

Main Results:

  • MSK1-activating kinases enhanced GRE-regulated promoter activity in a concentration-dependent manner.
  • Inhibition of MSK1 or MAPKs diminished maximal GR-mediated activity but enhanced sub-maximal activity.
  • Glucocorticoid-induced MSK1 translocation into the nucleus was concentration-dependent.

Conclusions:

  • MSK1 and MAPK activity exert complex, concentration-dependent effects on GR transactivation.
  • The findings reveal a nuanced interplay between kinase signaling and GR function.
  • Further research is needed to explore combined glucocorticoid and kinase inhibitor strategies for anti-inflammatory applications.
Keywords:
Concentration-dependent effectGlucocorticoid receptorMAPK (Mitogen-activated protein kinase)MSK1 (Mitogen- and stress-activated protein kinase 1)Transactivation

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