Interaction of glucocorticoid receptor isoforms with transcription factors AP-1 and NF-κB: Lack of effect of glucocorticoid receptor β

Iain J. Brogan, Iain Alexander Murray, Georgia Cerillo, Maurice Needham, Anne White, Julian R.E. Davis

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Glucocorticoids act through the glucocorticoid receptor (GR) to enhance or repress transcription of glucocorticoid responsive genes depending on the promoter context and cellular background. The human GR primary transcript is alternatively spliced resulting in hGRα and hGRβ isoforms. Transactivation and transrepression are mediated by hGRα and while it has been demonstrated that hGRβ, can act as a dominant negative inhibitor of hGRα mediated transactivation, its effects on transrepression are not known. To investigate hGRβ actions, we used GR-deficient COS-7 and HEK-293 cells. When hGRα (0.5 μg 106 cells-1) was transfected into COS-7 cells dexamethasone (150 nM) inhibited TNFα (80 U ml-1) effects on a NF-κB responsive reporter gene by 40%. There was no evidence of a dominant negative effect when hGRβ (1-10 μg) was co-transfected with hGRα up to ratios of 10:1. Similarly hGRβ had no effect on hGRα inhibition of a phorbol ester stimulated Ap-1-responsive reporter gene in COS-7 or HEK-293 cells. In comparison, an apparent dominant negative effect of hGRβ on hGRα-mediated transactivation was found to be attributable to non-specific transcriptional squelching in COS-7 cells. In summary, the potential for hGRβ, to act as a dominant negative inhibitor of hGRα-mediated transactivation remains controversial, but our data suggest that hGRβ, was unable to act as a dominant negative inhibitor of either hGRα-mediated transrepression or transactivation in these promoter and cell contexts. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume157
Issue number1-2
DOIs
StatePublished - Nov 25 1999

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this