Altered Subcellular Distribution of MSK1 Induced by Glucocorticoids Contributes to NF-kappaB Inhibition

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2008 May 31

PMID 18511904

Citations 45

Authors

Ilse M E Beck

Wim Vanden Berghe

Linda Vermeulen

Nadia Bougarne

Bert Vander Cruyssen

Guy Haegeman

Karolien De Bosscher

Affiliations

Soon will be listed here.

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.

Citing Articles

HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B.

Malvi P, Chava S, Cai G, Hu K, Zhu L, Edwards Y Cell Rep Med. 2023; 4(11):101285.

PMID: 37951219 PMC: 10694669. DOI: 10.1016/j.xcrm.2023.101285.

Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit.

Zhang J, Ge P, Liu J, Luo Y, Guo H, Zhang G Int J Mol Sci. 2023; 24(15).

PMID: 37569514 PMC: 10418884. DOI: 10.3390/ijms241512138.

Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor.

Pinheiro E, Preato A, Petrucci T, Santos L, Glezer I Front Endocrinol (Lausanne). 2023; 14:1160238.

PMID: 37124728 PMC: 10145926. DOI: 10.3389/fendo.2023.1160238.

Physiological Convergence and Antagonism Between GR and PPARγ in Inflammation and Metabolism.

Dacic M, Shibu G, Rogatsky I Adv Exp Med Biol. 2022; 1390:123-141.

PMID: 36107316 DOI: 10.1007/978-3-031-11836-4_7.

α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways.

Hight-Warburton W, Felix R, Burton A, Maple H, Chegkazi M, Steiner R Front Cell Dev Biol. 2021; 9:750771.

PMID: 34900996 PMC: 8655878. DOI: 10.3389/fcell.2021.750771.

References

Zhong H, Voll R, Ghosh S . Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300. Mol Cell. 1998; 1(5):661-71. DOI: 10.1016/s1097-2765(00)80066-0. View

Barnes P, Chung K, Page C . Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998; 50(4):515-96. View

Nissen R, Yamamoto K . The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev. 2000; 14(18):2314-29. PMC: 316928. DOI: 10.1101/gad.827900. View

Savory J, Hsu B, Laquian I, GIFFIN W, Reich T, Hache R . Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor. Mol Cell Biol. 1999; 19(2):1025-37. PMC: 116033. DOI: 10.1128/MCB.19.2.1025. View

John S, Sabo P, Johnson T, Sung M, Biddie S, Lightman S . Interaction of the glucocorticoid receptor with the chromatin landscape. Mol Cell. 2008; 29(5):611-24. DOI: 10.1016/j.molcel.2008.02.010. View

De Bosscher K, Vanden Berghe W, Haegeman G . Cross-talk between nuclear receptors and nuclear factor kappaB. Oncogene. 2006; 25(51):6868-86. DOI: 10.1038/sj.onc.1209935. View

Hager G, Elbi C, Becker M . Protein dynamics in the nuclear compartment. Curr Opin Genet Dev. 2002; 12(2):137-41. DOI: 10.1016/s0959-437x(02)00278-2. View

Gorlich D, Kutay U . Transport between the cell nucleus and the cytoplasm. Annu Rev Cell Dev Biol. 1999; 15:607-60. DOI: 10.1146/annurev.cellbio.15.1.607. View

Caelles C, Gonzalez-Sancho J, Munoz A . Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1998; 11(24):3351-64. PMC: 316827. DOI: 10.1101/gad.11.24.3351. View

10.

Hache R, Tse R, Reich T, Savory J, Lefebvre Y . Nucleocytoplasmic trafficking of steroid-free glucocorticoid receptor. J Biol Chem. 1999; 274(3):1432-9. DOI: 10.1074/jbc.274.3.1432. View

11.

Irusen E, Matthews J, Takahashi A, Barnes P, Chung K, Adcock I . p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002; 109(4):649-57. DOI: 10.1067/mai.2002.122465. View

12.

De Bosscher K, Vanden Berghe W, Vermeulen L, Plaisance S, Boone E, Haegeman G . Glucocorticoids repress NF-kappaB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. Proc Natl Acad Sci U S A. 2000; 97(8):3919-24. PMC: 18117. DOI: 10.1073/pnas.97.8.3919. View

13.

Pierreux C, Nicolas F, Hill C . Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus. Mol Cell Biol. 2000; 20(23):9041-54. PMC: 86557. DOI: 10.1128/MCB.20.23.9041-9054.2000. View

14.

De Bosscher K, Vanden Berghe W, Haegeman G . The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression. Endocr Rev. 2003; 24(4):488-522. DOI: 10.1210/er.2002-0006. View

15.

De Bosscher K, Vanden Berghe W, Beck I, Van Molle W, Hennuyer N, Hapgood J . A fully dissociated compound of plant origin for inflammatory gene repression. Proc Natl Acad Sci U S A. 2005; 102(44):15827-32. PMC: 1276063. DOI: 10.1073/pnas.0505554102. View

16.

Deak M, Clifton A, Lucocq L, Alessi D . Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998; 17(15):4426-41. PMC: 1170775. DOI: 10.1093/emboj/17.15.4426. View

17.

Dewint P, Gossye V, De Bosscher K, Vanden Berghe W, Van Beneden K, Deforce D . A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis. J Immunol. 2008; 180(4):2608-15. DOI: 10.4049/jimmunol.180.4.2608. View

18.

Garside H, Stevens A, Farrow S, Normand C, Houle B, Berry A . Glucocorticoid ligands specify different interactions with NF-kappaB by allosteric effects on the glucocorticoid receptor DNA binding domain. J Biol Chem. 2004; 279(48):50050-9. DOI: 10.1074/jbc.M407309200. View

19.

Chen P, Li J, Barnes J, Kokkonen G, Lee J, Liu Y . Restraint of proinflammatory cytokine biosynthesis by mitogen-activated protein kinase phosphatase-1 in lipopolysaccharide-stimulated macrophages. J Immunol. 2002; 169(11):6408-16. DOI: 10.4049/jimmunol.169.11.6408. View

20.

Robbins J, Dilworth S, Laskey R, Dingwall C . Two interdependent basic domains in nucleoplasmin nuclear targeting sequence: identification of a class of bipartite nuclear targeting sequence. Cell. 1991; 64(3):615-23. DOI: 10.1016/0092-8674(91)90245-t. View