Identification of Nuclear Receptor Interacting Proteins Using Yeast Two- Hybrid Technology

Applications to Drug Discovery
  • Sunil Nagpal
  • Corine R. Ghosn
  • Roshantha A. S. Chandraratna
Part of the Methods in Molecular Biology™ book series (MIMB, volume 176)


The yeast two-hybrid system is a powerful tool for the isolation and characterization of nuclear receptor interacting proteins such as coactivator and corepressor proteins. Generally coactivators associate with the nuclear receptors in an agonist-dependent manner and this specific protein-protein interaction forms the basis for ligand-mediated transcriptional activation of the target hormone-responsive genes. The association of corepressors with unliganded nuclear receptors allows the target genes to be in a repressed state in the absence of agonists. However depending on the stoichiometry of nuclear receptor coactivator and corepressor proteins in a given cell some degree of receptor/ coactivator interaction can occur resulting in a basal level of gene transcription. The ability of antagonists to maintain this basal equilibrium interaction or to increase receptor-corepressor interaction will determine whether they function as neutral antagonists or inverse agonists.


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Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Sunil Nagpal
    • 1
  • Corine R. Ghosn
    • 1
  • Roshantha A. S. Chandraratna
    • 2
  1. 1.Retinoid Research Department of BiologyAllergan Inc.Irvine
  2. 2.Retinoid Research Departments of Biology and ChemistryAllergan Inc.Irvine

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