Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling

Steven A. Kliewer, Kazuhiko Umesono, Richard A. Heyman, David J. Mangelsdorf, Jacqueline A. Dyck, Ronald M. Evans

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

We have recently described the properties of direct repeats (DRs) of the half-site AGGTCA as hormone response elements (HREs). According to our results, spacing the half sites by 3, 4, or 5 nucleotides determines specificity of response for vitamin D3, thyroid hormone, and retinoic acid receptors, respectively. This so-called 3-4-5 rule led to the prediction that remaining spacing options of 0, 1, and 2 might serve as targets for other nuclear receptors. A concurrent prediction is that receptors recognizing common sites might display more complex or combinatorial interactions. In exploring these predictions, we discovered that both the retinoid X receptor (RXR) and COUP-TF bind preferentially to a DR-1 motif. In vivo, RXR and COUP-TF display antagonistic action such that RXR-mediated activation is fully repressed by COUP-TF. In vitro studies reveal that COUP-TF and RXR form heterodimers on DR-1. Thus, these results support a general proposal in which the half-site spacing preferences may be used as a means to decipher potentially complex and interactive regulatory circuits.

Original languageEnglish (US)
Pages (from-to)1448-1452
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number4
StatePublished - Feb 15 1992

Fingerprint

Retinoid X Receptors
Tretinoin
Nucleic Acid Repetitive Sequences
Retinoic Acid Receptors
Cholecalciferol
Response Elements
Cytoplasmic and Nuclear Receptors
Thyroid Hormones
Nucleotides
Hormones

Keywords

  • Heterodimer
  • Hormone response element
  • Orphan receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. / Kliewer, Steven A.; Umesono, Kazuhiko; Heyman, Richard A.; Mangelsdorf, David J.; Dyck, Jacqueline A.; Evans, Ronald M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 4, 15.02.1992, p. 1448-1452.

Research output: Contribution to journalArticle

Kliewer, Steven A. ; Umesono, Kazuhiko ; Heyman, Richard A. ; Mangelsdorf, David J. ; Dyck, Jacqueline A. ; Evans, Ronald M. / Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 4. pp. 1448-1452.
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