Glucocorticoid receptor (GR) β has intrinsic, GRα-independent transcriptional activity

Tomoshige Kino, Irini Manoli, Sujata Kelkar, Yonghong Wang, Yan A. Su, George P. Chrousos

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The human glucocorticoid receptor (GR) gene produces C-terminal GRβ and GRα isoforms through alternative use of specific exons 9β and α, respectively. We explored the transcriptional activity of GRβ on endogenous genes by developing HeLa cells stably expressing EGFP-GRβ or EGFP. Microarray analyses revealed that GRβ had intrinsic gene-specific transcriptional activity, regulating mRNA expression of a large number of genes negatively or positively. Majority of GRβ-responsive genes was distinct from those modulated by GRα, while GRβ and GRα mutually modulated each other's transcriptional activity in a subpopulation of genes. We did not observe in HCT116 cells nuclear translocation of GRβ and activation of this receptor by RU 486, a synthetic steroid previously reported to bind GRβ and to induce nuclear translocation. Our results indicate that GRβ has intrinsic, GRα-independent, gene-specific transcriptional activity, in addition to its previously reported dominant negative effect on GRα-induced transactivation of GRE-driven promoters.

Original languageEnglish
Pages (from-to)671-675
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume381
Issue number4
DOIs
Publication statusPublished - 17 Apr 2009
Externally publishedYes

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Keywords

  • Gene expression
  • GR gene splicing variant
  • Nuclear translocation
  • RU 486

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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