Transcriptional Interference Between c-Jun and the Glucocorticoid Receptor: Mutual Inhibition of DNA Binding Due to Direct Protein-Protein Interaction

Cell. 1990 Sep 21;62(6):1205-15. doi: 10.1016/0092-8674(90)90396-v.

Abstract

Glucocorticoids are potent inhibitors of collagenase induction by phorbol esters and inflammatory mediators. The target for this negative effect is the AP-1 site within the collagenase promoter, which also mediates its induction. Negative regulation is due to repression of AP-1 activity by the glucocorticoid receptor (GCR). While the GCR is a potent inhibitor of AP-1 activity (Jun/Fos), both c-Jun and c-Fos are potent repressors of GCR activity. In vitro experiments using purified GCR and c-Jun proteins suggest that mutual repression is due to direct interaction between the two. Direct interaction between GCR and either c-Jun or c-Fos is demonstrated by cross-linking and coimmunoprecipitation. These findings reveal a cross talk between two major signal transduction systems used to control gene transcription in response to extracellular stimuli, and a novel mechanism for transcriptional repression.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation, Enzymologic
  • HeLa Cells / drug effects
  • HeLa Cells / enzymology
  • Humans
  • Microbial Collagenase / biosynthesis
  • Microbial Collagenase / genetics*
  • Plasmids
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogenes*
  • Receptors, Glucocorticoid / physiology*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic* / drug effects
  • Transfection

Substances

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