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Negative regulation of ERRα by a novel nucleolar protein

Soo-Jong Um1, Hyesook Youn, Eun-Joo Kim

  • 1Department of Bioscience & Biotechnology/Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747, Republic of Korea.

Biochemical and Biophysical Research Communications
|January 24, 2012
PubMed

Insights

A novel protein, retinoic acid resistance factor (RaRF), binds to estrogen-related receptor alpha (ERRα). RaRF sequesters ERRα in the nucleolus, inhibiting its transcriptional activity and target gene expression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Endocrinology

Background:

  • Estrogen-related receptors (ERRs) are nuclear receptors involved in various physiological processes.
  • The precise mechanisms regulating ERR transcriptional activity remain largely unknown.
  • Identifying interacting proteins is crucial for understanding ERR regulation.

Purpose of the Study:

  • To identify proteins that bind to estrogen-related receptor alpha (ERRα).
  • To elucidate the functional role of identified binding partners in ERRα transcriptional regulation.
  • To investigate the subcellular localization changes of ERRα upon interaction with binding partners.

Main Methods:

  • Yeast two-hybrid screening to identify ERRα-interacting proteins.
  • In vitro GST pull-down assays and immunoprecipitation (IP) in mammalian cells to confirm interactions.
  • Luciferase reporter assays to assess transcriptional activity.
  • shRNA-mediated knockdown to evaluate the effect of RaRF on ERRα activity.
  • Fluorescence microscopy to determine subcellular localization.

Main Results:

  • A novel protein, retinoic acid resistance factor (RaRF), was identified as an ERRα-binding protein.
  • RaRF specifically interacts with the C-terminus of ERRα.
  • RaRF expression inhibits ERRα transcriptional activity and represses the expression of the ERR target gene pS2.
  • RaRF induces the translocation of ERRα, but not ERRγ, to the nucleolus.

Conclusions:

  • Retinoic acid resistance factor (RaRF) directly binds to and inhibits estrogen-related receptor alpha (ERRα) transcriptional activity.
  • RaRF sequesters ERRα in the nucleolus, providing a novel mechanism for ERRα regulation.
  • These findings offer new insights into the molecular mechanisms governing ERRα function in gene regulation.

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