Modulation of Soluble Receptor Signaling by Coregulators

Coregulators are important cellular factors that allow nuclear receptors, the biological sensors of xenobiotic and endobiotic stimuli, to efficiently and appropriately mediate or repress gene expression. These factors can be singular units or multimeric complexes that can be divided into two categories: coactivators, which enhance receptor-target gene expression, and corepressors. Coactivators and corepressors utilize various protein-protein interaction domains to associate with cognate receptors and other transcription factors. During gene activation the disassembly of a repressor complex and its replacement with active transcription factor complexes is a tightly controlled process that is regulated in a context specific manner. Cell-type specific expression of certain coregulators can contribute to the level of response obtained upon nuclear receptor activation, as well as overall cell phenotype. As confirmed in null mouse model systems, the expression and control of coregulator activity is vital to normal physiological function and plays an influential role in disease. For example, amplification of the expression of certain coactivators in tumor cells can result in enhanced cell proliferation.