Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor

Cell. 1990 Sep 21;62(6):1217-26. doi: 10.1016/0092-8674(90)90397-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chromosome Deletion
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Dexamethasone / pharmacology*
  • HeLa Cells / metabolism
  • Humans
  • Microbial Collagenase / biosynthesis
  • Microbial Collagenase / genetics
  • Plasmids
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins c-jun
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / physiology*
  • Repressor Proteins / physiology
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic* / drug effects
  • Transfection


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-jun
  • Receptors, Glucocorticoid
  • Repressor Proteins
  • Transcription Factors
  • Dexamethasone
  • Protein-Tyrosine Kinases
  • Microbial Collagenase