title: Repression of glucocorticoid receptor gene transcription by c-Jun.
abstract: The regulation of glucocorticoid receptor gene expression by members of the AP-1 family was examined in glucocorticoid-free NIH3T3 cells transfected with the human glucocorticoid receptor gene promoter driving expression of a CAT reporter gene. c-Jun inhibited the promoter activity by 80% and JunB by 30%, whereas c-Fos and JunD had no inhibitory effect. Electrophoretic mobility 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 region containing the AP-1-like site was deleted. NIH3T3 cell clones overexpressing c-Jun exhibited lower glucocorticoid receptor mRNA levels, which suggests that the murine glucocorticoid receptor gene can also be regulated by AP-1. These results provide a new mechanism for cross-talk between the glucocorticoid receptor and the AP-1 family of transcription factors in the absence of glucocorticoid ligands.
authors.affiliation: Ludwig Institute for Cancer Research, 01509-900, São Paulo, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Cabral
authors.forename: A N
authors.initials: AN
authors.lastname: Hays
authors.forename: P R
authors.initials: PR
authors.lastname: Housley
authors.forename: M M
authors.initials: MM
authors.lastname: Brentani
authors.forename: V R
authors.initials: VR
authors.lastname: Martins
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1