The DNA binding-independent function of the glucocorticoid receptor mediates repression of AP-1-dependent genes in skin

Citation
Jp. Tuckermann et al., The DNA binding-independent function of the glucocorticoid receptor mediates repression of AP-1-dependent genes in skin, J CELL BIOL, 147(7), 1999, pp. 1365-1370
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
147
Issue
7
Year of publication
1999
Pages
1365 - 1370
Database
ISI
SICI code
0021-9525(199912)147:7<1365:TDBFOT>2.0.ZU;2-#
Abstract
The glucocorticoid receptor (GR) mediates the biological effects of glucoco rticoids (GCs) through activation or repression of gene expression, either by DNA binding or via interaction with other transcription factors, such as AP-1. Work in tissue culture cells on the regulation of AP-1-dependent gen es, such as collagenase (MMP-13) and stromelysin (MMP-3) has suggested that the antitumor and antiinflammatory activity of GCs is mediated, at least i n part, by GR-mediated downmodulation of AP-1. Here, we have identified pho rbol ester-induced expression of MMP-3 and MMP-13 in mouse skin as the firs t example of an in vivo system to measure negative interference between AP- 1 and GR in the animal. Cell type-specific induction of these genes by tumo r promoters is abolished by GCs. Importantly, this is also the case in GR(d im) mice expressing a DNA binding-defective mutant version of GR, In contra st, the newly identified target genes in skin, plasma glutathione peroxidas e and HSP-27, were induced by GC in wild-type, but not in GR(dim) mice. Thu s, these data suggest that the DNA binding-independent function of the GR i s dispensable for repression of AP-1 activity in vivo and responsible for t he antitumor promoting activity of GCs.