Agonist-bound nuclear receptors: Not just targets of coactivators

Abstract

Members of the nuclear receptor superfamily of ligand-regulated transcription factors are targets of a wide range of lipophilic signaling molecules as well as several drugs and xenobiotics that modulate many aspects of physiology and metabolism. Agonist binding to receptors is associated with recruitment of coactivators, which are essential for activation of target gene transcription. However, several biochemical and molecular genetic studies have shown that a full understanding of the function of agonist-bound receptors must also accommodate the recruitment of corepressors. These factors may attenuate agonist-induced transactivation, act more transiently as part of a cycle of cofactors recruited to target promoters by ligand-bound receptors, or function in hormone-dependent repression of target gene expression.