The small heterodimer partner interacts with the liver X receptor α and represses its transcriptional activity

Carole Brendel, Kristina Schoonjans, Oronza A. Botrugno, Eckardt Treuter, Johan Auwerx

Research output: Contribution to journalArticle

Abstract

The small heterodimer partner SHP (NROB2) is an unusual nuclear receptor that lacks the typical DNA binding domain common to most nuclear receptors. SHP has been reported to act as a corepressor for several nuclear receptors, but its exact mechanism of action is still elusive. Here we show that SHP can interact with the liver X receptors LXRα (NR1H3) and LXRβ (NR1H2), as demonstrated by glutathione-S-transferase pull-down assays, mammalian two-hybrid, and coimmunoprecipitation experiments. In transfection assays, SHP inhibits the expression of an artificial reporter driven by an LXR-response element and represses the transcriptional activation by LXR of the human ATP-binding cassette transporter 1 (ABCA1) promoter. Treatment of Caco-2 cells with bile acids, which activate farnesoid X receptor and subsequently induce SHP, leads to the repression of the human ABCG1 gene, an established LXR target gene. These results demonstrate that SHP is able to interact with LXR and to modulate its transcriptional activity.

Original languageEnglish
Pages (from-to)2065-2076
Number of pages12
JournalMolecular Endocrinology
Volume16
Issue number9
DOIs
Publication statusPublished - Sep 2002

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Cytoplasmic and Nuclear Receptors
ATP Binding Cassette Transporter 1
Co-Repressor Proteins
Two-Hybrid System Techniques
Caco-2 Cells
Response Elements
Glutathione Transferase
Bile Acids and Salts
Transcriptional Activation
Genes
Transfection
DNA
Liver X Receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

The small heterodimer partner interacts with the liver X receptor α and represses its transcriptional activity. / Brendel, Carole; Schoonjans, Kristina; Botrugno, Oronza A.; Treuter, Eckardt; Auwerx, Johan.

In: Molecular Endocrinology, Vol. 16, No. 9, 09.2002, p. 2065-2076.

Research output: Contribution to journalArticle

Brendel, Carole ; Schoonjans, Kristina ; Botrugno, Oronza A. ; Treuter, Eckardt ; Auwerx, Johan. / The small heterodimer partner interacts with the liver X receptor α and represses its transcriptional activity. In: Molecular Endocrinology. 2002 ; Vol. 16, No. 9. pp. 2065-2076.
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