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

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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