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Updated: Jun 23, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Nuclear receptors: genomic and non-genomic effects converge
Paloma Ordóñez-Morán1, Alberto Muñoz
1Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
Abstract:
The nuclear receptor superfamily mediates the regulatory activities of many hormones, nutrients and metabolites on the homeostasis and physiology of cells and tissues. Classically, ligand binding induced the ability of nuclear receptors to modulate the transcription rate of target genes (genomic effects), which led to consider them as ligand-activated transcription factors. Later, rapid actions of nuclear receptor ligands were reported that did not involve changes in gene expression. These (non-genomic) effects have been attributed in some cases to receptors different to those mediating gene transcription but most evidences indicate that they result from the activity of a population of nuclear receptor molecules acting outside the cell nucleus. Recent studies on estrogen and vitamin D, and their receptors (ERalpha/beta, VDR) support now the idea that non-genomic and genomic effects may integrate in a unique mode of action of nuclear receptor ligands, in which the non-genomic effects constitute signaling pathways required for the effects at the genome level. Here, we will discuss these novel findings and also those indicating transcriptional regulation through ligand-dependent and -independent crosstalk of nuclear receptors with beta-catenin or VDR-interacting repressor (VDIR).
Insights
Nuclear receptors regulate cell functions through genomic and non-genomic effects. Novel findings suggest non-genomic actions are crucial signaling pathways for nuclear receptor ligands
Area of Science:
- Molecular Endocrinology
- Cellular Physiology
- Gene Regulation
Background:
- Nuclear receptors are key regulators of cellular homeostasis and physiology.
- Traditionally viewed as ligand-activated transcription factors mediating genomic effects.
- Emerging evidence points to rapid, non-genomic effects independent of gene expression changes.
Purpose of the Study:
- To review novel findings on nuclear receptor ligand actions.
- To explore the integration of genomic and non-genomic effects.
- To discuss novel transcriptional regulation mechanisms involving nuclear receptors.
Main Methods:
- Literature review of recent studies on estrogen and vitamin D receptors (ERalpha/beta, VDR).
- Analysis of evidence for nuclear receptor activity outside the cell nucleus.
- Examination of ligand-dependent and -independent crosstalk with other proteins.
Main Results:
- Non-genomic effects may act as essential signaling pathways for genomic actions of nuclear receptor ligands.
- Specific nuclear receptors (ERalpha/beta, VDR) exemplify this integrated mode of action.
- Nuclear receptors engage in crosstalk with beta-catenin and VDR-interacting repressor (VDIR) for transcriptional regulation.
Conclusions:
- Nuclear receptor ligand action is a unified process involving both genomic and non-genomic mechanisms.
- Non-genomic signaling pathways are integral to the nuclear receptor's role in gene regulation.
- Crosstalk with other proteins offers new insights into nuclear receptor-mediated transcriptional control.
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