Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors

C Song1, J M Kokontis, R A Hiipakka

  • 1Ben May Institute, Chicago, IL.

Insights

Ubiquitous receptor (UR) modulates gene activation in retinoic acid and thyroid hormone pathways. This nuclear receptor inhibits and stimulates reporter gene expression, suggesting a key role in cell growth and differentiation.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Nuclear receptors are crucial regulators of gene expression.
  • Ubiquitous receptor (UR) is a newly identified nuclear receptor family member.
  • UR is expressed across various cell types, indicating widespread function.

Purpose of the Study:

  • To characterize the DNA binding and functional properties of Ubiquitous Receptor (UR).
  • To investigate the role of UR in retinoic acid and thyroid hormone signaling pathways.
  • To determine how UR interacts with other nuclear receptors like retinoid X receptor alpha (RXR alpha).

Main Methods:

  • Cloning of the UR cDNA.
  • Coexpression of UR with other nuclear receptors (hRXR alpha, hRAR alpha, TR beta) in COS-1 cells.
  • Reporter gene assays using chloramphenicol acetyltransferase (CAT) linked to specific DNA response elements (DR-4, DR-5).

Main Results:

  • UR protein and mRNA are ubiquitously detected.
  • UR/hRXR alpha heterodimers bind to DR-4 elements.
  • UR inhibits gene activation by hRXR alpha and hRAR alpha in a DR-4-dependent manner.
  • UR can also inhibit activation by TR beta.
  • UR can stimulate DR-4-CAT expression in the presence of hRXR alpha, an effect modulated by thyroid hormone receptor.

Conclusions:

  • UR plays a significant role in modulating retinoic acid and thyroid hormone signaling.
  • UR's function in gene activation suggests involvement in cellular growth and differentiation processes.
  • UR acts as a key regulator within nuclear receptor signaling networks.

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