Large Scale Production of Nuclear Receptor Ligand-Binding Domains

The nuclear receptor superfamily is composed of over 150 inducible transcription factors, most of which (1 -2 ) do not have well characterized ligands to date. Nuclear receptors regulate promoters through specific protein-protein and protein-DNA interaction at their hormone response elements, and up-or downregulate their target genes in a ligand-dependent manner with the aid of various cofactors (2 -4 ). The high-affinity binding of ligands sets into action the complex signal transduction properties of these proteins. Ligand occupancy is a key determinant of function, because it can result in the formation of distinct molecular surfaces that have enhanced affinity for coactivators or corepressors (5 -7 ). However, additional levels of regulation can be achieved through interactions with other systems, such as molecular chaperones, cyclic adenosine monophosphate-regulated kinases and the AP-1 activator (8 -9 ). All of these interactions together form a rich and elaborate network by which the ligands ultimately exert their powerful effects on gene expression.