Identification of Nuclear Receptor Interacting Proteins Using Yeast Two-Hybrid Technology: Applications to Drug Discovery

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. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.