JUND ACTIVATES TRANSCRIPTION THROUGH MULTIPLE GRES IN THE ABSENCE OF ACTIVE GLUCOCORTICOID RECEPTOR

Transcription factor AP-1 and the glucocorticoid receptor activate gen e expression through interaction with specific DNA elements located in the promoter/enhancer region of responsive genes. Recently, it was re ported that AP-1 and the glucocorticoid receptor are able to mutually repress each others transcriptional activity. Both, Fos and Jun consis t of small families of genes coding for structurally related proteins. The inhibition of the glucocorticoid receptor activity by AP-1 was sh own for c-Fos and c-Jun. We extended these studies by investigating th e effects of JunD, JunB and FosB on the activity of the glucocorticoid receptor. We present evidence that co-transfection of a JunD expressi on vector and a glucocorticoid hormone-dependent gene construct contai ning 4 GREs (p4GRE(-37)Tk-CAT) results in a strong promoter activation by a hormone-independent mechanism. The effect seems to be restricted to JunD (and to some extent FosB) whereas c-Fos, c-Jun or JunB do not mediate a significant stimulation of the p4GRE (-37)Tk-CAT construct in similar transfection assays. The JunD mediated activation of the p4 GRE(-37)Tk-CAT is independent of the normal glucocorticoid response si nce a similar activation is observed in CV-1 cells deficient in functi onal glucocorticoid receptor. Finally, we show that in NIH 3T3 cells t he JunD mediated transactivation through TRE elements is inhibited by dexamethasone.