This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Bosscher, K. Articles by Haegeman, G. Search for Related Content PubMed PubMed Citation Articles by De Bosscher, K. Articles by Haegeman, G.

Glucocorticoid Repression of AP-1 Is Not Mediated by Competition for Nuclear Coactivators

Department of Molecular Biology University of Gent-VIB 9000 Gent, Belgium

Interleukin-6 (IL-6) is a pleiotropic cytokine that is involved in many autoimmune and inflammatory diseases. Transcriptional control of IL-6 gene expression is exerted by various compounds, among which glucocorticoids are the most potent antiinflammatory and immunosuppressive agents currently in use. Glucocorticoids exert their transrepressive actions by negatively interfering with transcription factors, such as nuclear factor-B (NF-B) and AP-1. Both factors make use of the coactivator cAMP response element-binding protein (CREB)-binding protein (CBP) to enhance their transcriptional activities, which led to the hypothesis that a mutual antagonism between p65 or c-Jun and activated glucocorticoid receptor (GR) results from a limited amount of CBP. Recently, we showed that glucocorticoid repression of NF-B-driven gene expression occurs irrespective of the amount of coactivator levels in the cell. In the current study, we extend this observation and demonstrate that also AP-1-targeted gene repression by glucocorticoids is refractory to increased amounts of nuclear coactivators. From results with Gal4 chimeric proteins we conclude that glucocorticoid repression occurs by a promoter-independent mechanism involving a nuclear interplay between activated GR and AP-1, independently of CBP levels in the cell.

This article has been cited by other articles:

				R. Newton and N. S. Holden Separating Transrepression and Transactivation: A Distressing Divorce for the Glucocorticoid Receptor? Mol. Pharmacol., October 1, 2007; 72(4): 799 - 809. [Abstract] [Full Text] [PDF]

				M. Verras, J. Lee, H. Xue, T.-H. Li, Y. Wang, and Z. Sun The Androgen Receptor Negatively Regulates the Expression of c-Met: Implications for a Novel Mechanism of Prostate Cancer Progression Cancer Res., February 1, 2007; 67(3): 967 - 975. [Abstract] [Full Text] [PDF]

				P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet Overview of Nomenclature of Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 685 - 704. [Abstract] [Full Text] [PDF]

				C. Martens, S. Bilodeau, M. Maira, Y. Gauthier, and J. Drouin Protein-Protein Interactions and Transcriptional Antagonism between the Subfamily of NGFI-B/Nur77 Orphan Nuclear Receptors and Glucocorticoid Receptor Mol. Endocrinol., April 1, 2005; 19(4): 885 - 897. [Abstract] [Full Text] [PDF]

				L.-G. Bladh, J. Liden, K. Dahlman-Wright, M. Reimers, S. Nilsson, and S. Okret Identification of Endogenous Glucocorticoid Repressed Genes Differentially Regulated by a Glucocorticoid Receptor Mutant Able to Separate between Nuclear Factor-{kappa}B and Activator Protein-1 Repression Mol. Pharmacol., March 1, 2005; 67(3): 815 - 826. [Abstract] [Full Text] [PDF]

				A Cote-Velez, L Perez-Martinez, M Y Diaz-Gallardo, C Perez-Monter, A Carreon-Rodriguez, J-L Charli, and P Joseph-Bravo Dexamethasone represses cAMP rapid upregulation of TRH gene transcription: identification of a composite glucocorticoid response element and a cAMP response element in TRH promoter J. Mol. Endocrinol., February 1, 2005; 34(1): 177 - 197. [Abstract] [Full Text] [PDF]

				B. M. Necela and J. A. Cidlowski Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells Proceedings of the ATS, November 1, 2004; 1(3): 239 - 246. [Full Text] [PDF]

				G. Haegeman Inhibition of signal transduction pathways involved in inflammation Eur. Respir. J., September 20, 2003; 22(44_suppl): 16s - 19s. [Full Text] [PDF]

				K. De Bosscher, W. Vanden Berghe, and G. Haegeman The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression Endocr. Rev., August 1, 2003; 24(4): 488 - 522. [Abstract] [Full Text] [PDF]

				C.-T. Yu, M.-H. L. Feng, H.-m. Shih, and M.-Z. Lai Increased p300 Expression Inhibits Glucocorticoid Receptor-T-Cell Receptor Antagonism but Does Not Affect Thymocyte Positive Selection Mol. Cell. Biol., July 1, 2002; 22(13): 4556 - 4566. [Abstract] [Full Text] [PDF]

				S. Greenstein, K. Ghias, N. L. Krett, and S. T. Rosen Mechanisms of Glucocorticoid-mediated Apoptosis in Hematological Malignancies Clin. Cancer Res., June 1, 2002; 8(6): 1681 - 1694. [Abstract] [Full Text] [PDF]

				W. Y. Almawi and O. K. Melemedjian Molecular mechanisms of glucocorticoid antiproliferative effects: antagonism of transcription factor activity by glucocorticoid receptor J. Leukoc. Biol., January 1, 2002; 71(1): 9 - 15. [Abstract] [Full Text] [PDF]