Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor

Roland Schüle, Pundl Rangarajan, Steven Kliewer, Lynn J. Ransone, Jack Bolado, Na Yang, Inder M. Verma, Ronald M. Evans

Research output: Contribution to journalArticlepeer-review

1007 Scopus citations

Abstract

We present evidence that the glucocorticoid receptor (GR) and transcription factor Jun/AP-1 can reciprocally repress one another's transcriptional activation by a novel mechanism that is Independent of DNA binding. Overexpression of c-Jun prevents the glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element (GRE). Conversely, GR is able to repress AP-1-mediated transcriptional activation. Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression. Gel retardation analysis demonstrates that bacterially expressed c-Jun disrupts GR-GRE complexes. These data Indicate that members of two distinct classes of transcription factors can oppose one another's activity through a mechanism likely involving protein-protein interactions.

Original languageEnglish (US)
Pages (from-to)1217-1226
Number of pages10
JournalCell
Volume62
Issue number6
DOIs
StatePublished - Sep 21 1990

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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