The DNA Binding-Independent Function of the Glucocorticoid Receptor Mediates Repression of Ap-1-Dependent Genes in Skin

doi:10.1083/jcb.147.7.1365

This Article

	Full Text
	Full Text (PDF, 286K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Tuckermann, J. P.
	Articles by Angel, P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Tuckermann, J. P.
	Articles by Angel, P.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/1999//1365 $5.00
The Journal of Cell Biology, Volume 147, Number 7, , 1999 1365-1370

Brief Report

The DNA Binding-Independent Function of the Glucocorticoid Receptor Mediates Repression of Ap-1–Dependent Genes in Skin

Jan P. Tuckermann^a, Holger M. Reichardt^b, Rosa Arribas^b, K. Hartmut Richter^a, Günther Schütz^b, and Peter Angel^a

^a Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany
^b Division of Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany
Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.49 6221-42-455449 6221-42-4570

p.angel{at}dkfz-heidelberg.de

The glucocorticoid receptor (GR) mediates the biological effectsof glucocorticoids (GCs) through activation or repression ofgene expression, either by DNA binding or via interaction withother transcription factors, such as AP-1. Work in tissue culturecells on the regulation of AP-1–dependent genes, suchas collagenase (MMP-13) and stromelysin (MMP-3) has suggestedthat the antitumor and antiinflammatory activity of GCs is mediated,at least in part, by GR-mediated downmodulation of AP-1. Here,we have identified phorbol ester-induced expression of MMP-3and MMP-13 in mouse skin as the first example of an in vivosystem to measure negative interference between AP-1 and GRin the animal. Cell type-specific induction of these genes bytumor promoters is abolished by GCs. Importantly, this is alsothe case in GR^dim mice expressing a DNA binding-defective mutantversion of GR. In contrast, the newly identified target genesin skin, plasma glutathione peroxidase and HSP-27, were inducedby GC in wild-type, but not in GR^dim mice. Thus, these datasuggest that the DNA binding-independent function of the GRis dispensable for repression of AP-1 activity in vivo and responsiblefor the antitumor promoting activity of GCs.

Key Words: tumor promotion • mouse skin • AP-1 • matrix metalloproteinase • collagenase • glucocorticoid receptor • GR^dim

Jan P. Tuckermann's present address is Division of MolecularBiology of the Cell I, Deutsches Krebsforschungszentrum, D-69120Heidelberg, Germany.

Abbreviations used in this paper: GCs, glucocorticoids; GR,glucocorticoid receptor; GR^dim, mice homozygous for a mutationin the endogenous GR gene; GRE, GR responsive element; MMP,matrix metalloproteinase; PGX-3, plasma glutathione peroxidase-3;TPA, 12-O-tetradecanoyl-phorbol-13-acetate.

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Facebook

Technorati

Twitter What's this?

This article has been cited by other articles:

Bogdarina, I. G, King, P. J, Clark, A. J L (2009). Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids. J Mol Endocrinol 43: 73-80 [Abstract] [Full Text]
De Bosscher, K., Haegeman, G. (2009). Minireview: Latest Perspectives on Antiinflammatory Actions of Glucocorticoids. Mol. Endocrinol. 23: 281-291 [Abstract] [Full Text]
Diefenbacher, M., Sekula, S., Heilbock, C., Maier, J. V., Litfin, M., van Dam, H., Castellazzi, M., Herrlich, P., Kassel, O. (2008). Restriction to Fos Family Members of Trip6-Dependent Coactivation and Glucocorticoid Receptor-Dependent Trans-Repression of Activator Protein-1. Mol. Endocrinol. 22: 1767-1780 [Abstract] [Full Text]
Donet, E., Bosch, P., Sanchis, A., Bayo, P., Ramirez, A., Cascallana, J. L., Bravo, A., Perez, P. (2008). Transrepression Function of the Glucocorticoid Receptor Regulates Eyelid Development and Keratinocyte Proliferation but Is Not Sufficient to Prevent Skin Chronic Inflammation. Mol. Endocrinol. 22: 799-812 [Abstract] [Full Text]
Bayo, P., Sanchis, A., Bravo, A., Cascallana, J. L., Buder, K., Tuckermann, J., Schutz, G., Perez, P. (2008). Glucocorticoid Receptor Is Required for Skin Barrier Competence. Endocrinology 149: 1377-1388 [Abstract] [Full Text]
Newton, R., Holden, N. S. (2007). Separating Transrepression and Transactivation: A Distressing Divorce for the Glucocorticoid Receptor?. Mol. Pharmacol. 72: 799-809 [Abstract] [Full Text]
Sainte Marie, Y., Toulon, A., Paus, R., Maubec, E., Cherfa, A., Grossin, M., Descamps, V., Clemessy, M., Gasc, J.-M., Peuchmaur, M., Glick, A., Farman, N., Jaisser, F. (2007). Targeted Skin Overexpression of the Mineralocorticoid Receptor in Mice Causes Epidermal Atrophy, Premature Skin Barrier Formation, Eye Abnormalities, and Alopecia. Am. J. Pathol. 171: 846-860 [Abstract] [Full Text]
Edwards, M. R., Haas, J., Panettieri, R. A. Jr., Johnson, M., Johnston, S. L. (2007). Corticosteroids and beta2 Agonists Differentially Regulate Rhinovirus-induced Interleukin-6 via Distinct Cis-acting Elements. J. Biol. Chem. 282: 15366-15375 [Abstract] [Full Text]
Bhattacharyya, S., Brown, D. E., Brewer, J. A., Vogt, S. K., Muglia, L. J. (2007). Macrophage glucocorticoid receptors regulate Toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase. Blood 109: 4313-4319 [Abstract] [Full Text]
Wu, J., Bresnick, E. H. (2007). Glucocorticoid and Growth Factor Synergism Requirement for Notch4 Chromatin Domain Activation. Mol. Cell. Biol. 27: 2411-2422 [Abstract] [Full Text]
McMaster, A., Ray, D. W. (2007). Modelling the glucocorticoid receptor and producing therapeutic agents with anti-inflammatory effects but reduced side-effects. Exp Physiol 92: 299-309 [Abstract] [Full Text]
Abraham, S. M., Lawrence, T., Kleiman, A., Warden, P., Medghalchi, M., Tuckermann, J., Saklatvala, J., Clark, A. R. (2006). Antiinflammatory effects of dexamethasone are partly dependent on induction of dual specificity phosphatase 1. JEM 203: 1883-1889 [Abstract] [Full Text]
Baumann, S., Dostert, A., Novac, N., Bauer, A., Schmid, W., Fas, S. C., Krueger, A., Heinzel, T., Kirchhoff, S., Schutz, G., Krammer, P. H. (2005). Glucocorticoids inhibit activation-induced cell death (AICD) via direct DNA-dependent repression of the CD95 ligand gene by a glucocorticoid receptor dimer. Blood 106: 617-625 [Abstract] [Full Text]
Gebhardt, C., Breitenbach, U., Richter, K. H., Furstenberger, G., Mauch, C., Angel, P., Hess, J. (2005). c-Fos-Dependent Induction of the Small Ras-Related GTPase Rab11a in Skin Carcinogenesis. Am. J. Pathol. 167: 243-253 [Abstract] [Full Text]
Simard, J., Ricketts, M.-L., Gingras, S., Soucy, P., Feltus, F. A., Melner, M. H. (2005). Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family. Endocr. Rev. 26: 525-582 [Abstract] [Full Text]
Leis, H., Page, A., Ramirez, A., Bravo, A., Segrelles, C., Paramio, J., Barettino, D., Jorcano, J. L., Perez, P. (2004). Glucocorticoid Receptor Counteracts Tumorigenic Activity of Akt in Skin through Interference with the Phosphatidylinositol 3-Kinase Signaling Pathway. Mol. Endocrinol. 18: 303-311 [Abstract] [Full Text]
Kodama, T., Shimizu, N., Yoshikawa, N., Makino, Y., Ouchida, R., Okamoto, K., Hisada, T., Nakamura, H., Morimoto, C., Tanaka, H. (2003). Role of the Glucocorticoid Receptor for Regulation of Hypoxia-dependent Gene Expression. J. Biol. Chem. 278: 33384-33391 [Abstract] [Full Text]
De Bosscher, K., Vanden Berghe, W., Haegeman, G. (2003). The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression. Endocr. Rev. 24: 488-522 [Abstract] [Full Text]
Mittelstadt, P. R., Ashwell, J. D. (2003). Disruption of Glucocorticoid Receptor Exon 2 Yields a Ligand-Responsive C-Terminal Fragment that Regulates Gene Expression. Mol. Endocrinol. 17: 1534-1542 [Abstract] [Full Text]
Almawi, W. Y., Melemedjian, O. K. (2002). Molecular mechanisms of glucocorticoid antiproliferative effects: antagonism of transcription factor activity by glucocorticoid receptor. J. Leukoc. Biol. 71: 9-15 [Abstract] [Full Text]
Doppler, W., Windegger, M., Soratroi, C., Tomasi, J., Lechner, J., Rusconi, S., Cato, A. C. B., Almlöf, T., Liden, J., Okret, S., Gustafsson, J.-A., Richard-Foy, H., Starr, D. B., Klocker, H., Edwards, D., Geymayer, S. (2001). Expression Level-Dependent Contribution of Glucocorticoid Receptor Domains for Functional Interaction with STAT5. Mol. Cell. Biol. 21: 3266-3279 [Abstract] [Full Text]
De Bosscher, K., Vanden Berghe, W., Haegeman, G. (2001). Glucocorticoid Repression of AP-1 Is Not Mediated by Competition for Nuclear Coactivators. Mol. Endocrinol. 15: 219-227 [Abstract] [Full Text]
Gonzalez, M. V., Jimenez, B., Berciano, M. T., Gonzalez-Sancho, J. M., Caelles, C., Lafarga, M., Munoz, A. (2000). Glucocorticoids Antagonize Ap-1 by Inhibiting the Activation/Phosphorylation of Jnk without Affecting Its Subcellular Distribution. JCB 150: 1199-1208 [Abstract] [Full Text]
Schinner, S., Dellas, C., Schroder, M., Heinlein, C. A., Chang, C., Fischer, J., Knepel, W. (2002). Repression of Glucagon Gene Transcription by Peroxisome Proliferator-activated Receptor gamma through Inhibition of Pax6 Transcriptional Activity. J. Biol. Chem. 277: 1941-1948 [Abstract] [Full Text]