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ERAP140, a conserved tissue-specific nuclear receptor coactivator.

Wenlin Shao1, Shlomit Halachmi, Myles Brown

  • 1Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

Molecular and Cellular Biology
|April 25, 2002
PubMed
Summary

We discovered ERAP140, a new nuclear receptor coactivator. This protein interacts with estrogen receptor alpha and enhances its activity, suggesting a distinct role in specific tissues.

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Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Nuclear receptors play crucial roles in gene regulation.
  • Coactivators are essential for modulating nuclear receptor activity.
  • The identification of novel coactivators is key to understanding complex signaling pathways.

Purpose of the Study:

  • To identify and characterize a novel nuclear receptor coactivator.
  • To investigate the interaction of ERAP140 with estrogen receptor alpha (ER alpha).
  • To determine the functional role of ERAP140 in nuclear receptor-mediated transcription.

Main Methods:

  • Protein interaction screening using ER alpha ligand binding domain.
  • Homology searches across different species.
  • Expression analysis in various cell and tissue types.
  • Co-immunoprecipitation and reporter gene assays to assess interactions and transcriptional activity.

Main Results:

  • ERAP140, a novel coactivator, was identified and characterized.
  • ERAP140 interacts with multiple nuclear receptors including ER alpha, ER beta, TR beta, PPAR gamma, and RAR alpha.
  • ERAP140 enhances the transcriptional activity of interacting nuclear receptors.
  • ERAP140 is recruited to target gene promoters by estrogen-bound ER alpha in vivo.

Conclusions:

  • ERAP140 represents a distinct class of nuclear receptor coactivators.
  • ERAP140 plays a significant role in mediating nuclear receptor signaling, particularly in the brain.
  • ERAP140's specific tissue distribution suggests targeted roles in receptor function.