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 famili es of transcription factors that convert extracellular signals into lo ng-term genetic responses. Despite clear differences in their modes of activation and DNA binding specificities, a regulatory cross-talk bet ween AP-1 and SHR such as the glucocorticoid receptor (CR), has been e stablished. 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 a nd is mediated through the DNA binding domain of Jun. Since individual subunits of AP-1 exhibit small differences in sequence specificity, s pecific subsets of AP-1-dependent genes may be regulated by steroid ho rmones in different directions.