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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Nuclear receptor corepressors

Mitchell A Lazar1

  • 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. lazar@mail.med.upenn.edu

Nuclear Receptor Signaling
|April 11, 2006
PubMed

Insights

Nuclear receptor (NR) ligand-binding domains (LBDs) interact with corepressor proteins to mediate repression. Yeast-two hybrid screens identified key corepressors, N-CoR and SMRT, crucial for understanding this mechanism.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Nuclear receptors (NRs) regulate gene expression.
  • Ligand-binding domains (LBDs) of NRs mediate repression.
  • Repression is thought to involve interactions with cellular corepressor proteins.

Purpose of the Study:

  • To review the isolation and characterization of corepressors.
  • To focus on the corepressors N-CoR and SMRT.
  • To discuss the role of NR LBDs in mediating repression.

Main Methods:

  • Yeast-two hybrid screens for protein interactors.
  • Functional transfer of repression assays.
  • Cross-squelching experiments.

Main Results:

  • NR LBDs can transfer repression function to heterologous DNA-binding domains.
  • Untethered LBDs can cross-squelch repression.
  • Yeast-two hybrid screens have been instrumental in identifying corepressors.

Conclusions:

  • Corepression by NRs is mediated by interactions with specific cellular proteins.
  • N-CoR and SMRT are key corepressors involved in NR-mediated gene silencing.
  • Further characterization of these corepressors is essential for understanding NR function.

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