Repression of glucocorticoid receptor gene transcription by c-Jun

The regulation of glucocorticoid receptor gene expression by members of the AP-1 family was examined in glucocorticoid-free NIH3T3 cells transfected w ith the human glucocorticoid receptor gene promoter driving expression of a CAT reporter gene. c-Jun inhibited the promoter activity by 80% and JunB b y 30%, whereas c-Fos and JunD had no inhibitory effect. Electrophoretic mob ility shift assays showed that c-Jun is unable to efficiently interact with the AP-1-like site present in the human glucocorticoid receptor promoter. Moreover, c-Jun was still able to repress promoter mutants in which the reg ion containing the AP-1-like site was deleted. NIH3T3 cell clones overexpre ssing c-Jun exhibited lower glucocorticoid receptor mRNA levels, which sugg ests that the murine glucocorticoid receptor gene can also be regulated by AP-1. These results provide a new mechanism for cross-talk between the gluc ocorticoid receptor and the AP-1 family of transcription factors in the abs ence of glucocorticoid ligands. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.