The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators

Tetsuya Tagami, Ward H. Lutz, Rajiv Kumar, J. Larry Jameson

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

The vitamin D receptor (VDR), thyroid hormone receptor (TR), and retinoic acid receptor (RAR) are ligand-dependent transcription factors that function via the formation of heterodimeric complexes with retinoid X receptor (RXR). Although TR and RAR are known to act as transcriptional repressors in the absence of cognate ligands, it is not clear whether VDR exhibits this property. Recently, transcriptional repression (basal silencing) by TR and RAR was shown to be mediated by nuclear receptor corepressors (CoRs), such as NCoR and SMRT. In this report, we examined the silencing ability of VDR and its interaction with NCoR and SMRT using mammalian two-hybrid assays. The Gal4-VDR fusion protein silenced the basal expression of a reporter that contains Gal4 binding sites, but the degree of silencing activity was weaker than that of Gal4-TR. In mammalian two-hybrid assays, the interaction of VP16-SMRT or VP16-NCoR was also stronger with Gal4-TR than with Gal4-VDR. Similar results were obtained when the assay was performed using the opposite configuration. Gal4-SMRT or Gal4-NCoR interacted better with VP16-TR than with VP16-VDR. These interactions were disrupted by the addition of cognate ligands. In contrast, VP16-VDR interacted better than VP16-TR when studied with a coactivator, Gal4-SRC1, or with the heterodimeric partner, Gal4-RXR. Consistent with these findings, relatively weak transcriptional silencing by the native VDR was observed using the osteopontin VDRE. Thus, in comparison to TR, VDR exhibits relatively weak ligand-independent transcriptional silencing, but it possesses strong dimerization with RXR and ligand-induced binding to transcriptional coactivators.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume253
Issue number2
DOIs
StatePublished - Dec 18 1998

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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