The glucocorticoid receptor synergizes with Jun homodimers to activate AP-1-regulated promoters lacking GR binding sites.
Jun/Fos (AP-1) and steroid hormone receptors (SHR) are distinct families of transcription factors that convert extracellular signals into long-term genetic responses. Despite clear differences in their modes of activation and DNA binding specificities, a regulatory cross-talk between AP-1 and SHR such as the glucocorticoid receptor (GR), has been established. Here, we show that the hormone-activated GR negatively or positively modulates the expression of AP-1-dependent genes, depending on the subunits of the dimeric AP-1 complex. This type of regulation does not depend on the presence of a GR binding site in the promoter and is mediated through the DNA binding domain of Jun. Since individual subunits of AP-1 exhibit small differences in sequence specificity, specific subsets of AP-1-dependent genes may be regulated by steroid hormones in different directions.
Teurich
S
S
Forschungszentrum Karlsruhe, Institut für Genetik, Germany.
Angel
P
P
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology*; D015533:Transcriptional Activation
D016759:Oncogene Protein p65(gag-jun); D016761:Oncogene Proteins v-fos; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D004247:DNA