Cell
Volume 62, Issue 6, 21 September 1990, Pages 1205-1215
Journal home page for Cell

Article
Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interaction

https://doi.org/10.1016/0092-8674(90)90396-VGet rights and content

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.

References (54)

  • A.E. Oro et al.

    Transcriptional inhibition by a glucocorticoid receptor-β-galactosidase fusion protein

    Cell

    (1988)
  • T.J. Schmidt et al.

    Thermal activation of the purified rat hepatic glucocorticoid receptor

    J. Biol. Chem.

    (1985)
  • I.E. Akerblom et al.

    Negative regulation by glucocorticoids through interference with cAMP responsive enhancer

    Science

    (1988)
  • P. Angel et al.

    12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′ flanking region

    Mol. Cell. Biol.

    (1987)
  • P. Angel et al.

    Oncogene jun encodes a sequence-specific trans-activator similar to AP-1

    Nature

    (1988)
  • P. Angel et al.

    Jun and v-Jun contain multiple regions that participate in transcriptional activation in an interdependent manner

    New Biol.

    (1989)
  • D. Bohmann et al.

    Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1

    Science

    (1987)
  • D.A. Brenner et al.

    Prolonged activation of jun and collagenase genes by tumor necrosis factor-alpha

    Nature

    (1989)
  • C.E. Brinckerhoff et al.

    Half-life of synovial cell collagenase mRNA is modulated by phorbol myristate acetate but not by all-trans retinoic acid or dexamethasone

    Biochemistry

    (1986)
  • C. Buchman et al.

    The CUP2 gene product, regulator of metallothionein expression, is a copper-activated DNA-binding protein

    Mol. Cell. Biol.

    (1989)
  • J. Charron et al.

    Glucocorticoid inhibition of transcription from episomal proopiomelanocortin gene promoter

  • W. Conca et al.

    Increases in levels of procollagenase mRNA in cultured fibroblasts induced by human recombinant interleukin-1 beta or serum follow c-jun expression and are dependent on new protein synthesis

    J. Clin. Invest.

    (1989)
  • T. Deng et al.

    A novel expression vector for high-level synthesis and secretion of foreign proteins in Escherichia coli: overproduction of bovine pancreatic phospholipase A2

    Gene

    (1990)
  • J.R. deWet et al.

    Firefly luciferase gene: structure and expression in mammalian cells

    Mol. Cell. Biol.

    (1987)
  • J. Drouin et al.

    Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent inhibition of proopiomelanocortin gene transcription

    Mol. Cell. Biol.

    (1989)
  • G. Gill et al.

    Negative effect of the transcriptional activator GAL4

    Nature

    (1988)
  • A.G. Gilman et al.

    Goodman and Gilman's The Pharmacological Basis of Therapeutics

    (1985)
  • Cited by (1463)

    • Glucocorticoids

      2021, Lahita’s Systemic Lupus Erythematosus
    View all citing articles on Scopus
    View full text