The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities

Implications for intermediary metabolism

Massimo U. De Martino, Nisan Bhattachryya, Salvatore Alesci, Takamasa Ichijo, George P. Chrousos, Tomoshige Kino

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Glucocorticoids exert their metabolic effect via their intracellular receptor, the glucocorticoid receptor (GR). In a yeast two-hybrid screening, we found the chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), an orphan nuclear receptor that plays important roles in glucose, cholesterol, and xenobiotic metabolism, as a partner of GR. In an in vitro glutathione-S-transferase pull-down assay, COUP-TFII interacted via its DNA-binding domain with the hinge regions of both GRα and its splicing variant GRβ, whereas COUP-TFII formed a complex with GRα, but not with GRβ, in an in vivo chromatin immunoprecipitation and a regular immunoprecipitation assay. Accordingly, GRα, but not GRβ, enhanced COUP-TFII-induced transactlvation of the simple COUP-TFII-responsive 7α-hydroxylase promoter through the transcriptlonal activity of its activation function-1 domain, whereas COUP-TFII repressed GRα-induced transactivation of the glucocorticoid-responsive promoter by attracting the silencing mediator for retinoid and thyroid hormone receptors. Importantly, mutual protein-protein interaction of GRα and COUP-TFII was necessary for glucocorticoid-induced enhancement of the promoter activity and the endogenous mRNA expression of the COUP-TFII-responsive phosphoenolpyruvate carboxykinase, the rate-limiting enzyme of hepatic gluconeogenesis. We suggest that COUP-TFII may participate in some of the metabolic effects of glucocorticoids through direct interactions with GRα. These interactions influence the transcription of both COUP-TFII- and GRα-responsive target genes, seem to be promoter specific, and can be in either a positive or negative direction.

Original languageEnglish
Pages (from-to)820-833
Number of pages14
JournalMolecular Endocrinology
Volume18
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

Fingerprint

COUP Transcription Factor II
Orphan Nuclear Receptors
Glucocorticoid Receptors
Glucocorticoids
Thyroid Hormone Receptors
Phosphoenolpyruvate
Gluconeogenesis
Chromatin Immunoprecipitation
Retinoids

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

The glucocorticoid receptor and the orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II interact with and mutually affect each other's transcriptional activities : Implications for intermediary metabolism. / De Martino, Massimo U.; Bhattachryya, Nisan; Alesci, Salvatore; Ichijo, Takamasa; Chrousos, George P.; Kino, Tomoshige.

In: Molecular Endocrinology, Vol. 18, No. 4, 04.2004, p. 820-833.

Research output: Contribution to journalArticle

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