Transcription factor AP-1 and the glucocorticoid receptor activate gene expression through interaction with specific DNA elements located in the promoter/enhancer region of responsive genes. Recently, it was reported that AP-1 and the glucocorticoid receptor are able to mutually repress each others transcriptional activity. Both, Fos and Jun consist of small families of genes coding for structurally related proteins. The inhibition of the glucocorticoid receptor activity by AP-1 was shown for c-Fos and c-Jun. We extended these studies by investigating the effects of JunD, JunB and FosB on the activity of the glucocorticoid receptor. We present evidence that co-transfection of a JunD expression vector and a glucocorticoid hormone-dependent gene construct containing 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 p4GRE(-37)Tk-CAT is independent of the normal glucocorticoid response since a similar activation is observed in CV-1 cells deficient in functional glucocorticoid receptor. Finally, we show that in NIH 3T3 cells the JunD mediated transactivation through TRE elements is inhibited by dexamethasone.

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