Chemical biology approaches to understanding the regulation of nuclear receptors

摘要

The nuclear receptor (NR) superfamily of ligand-dependent transcription factors regulate a large number of biological processes and are key targets for pharmacological intervention. The transcriptional activity of most NRs is regulated through binding of ligand followed by dissociation of co-repressor and association with heterodimer partner and/or coactivator. The response of NRs to synthetic and endogenous ligands allows their use as tools for dissecting the mechanisms of regulation. We have previously demonstrated how HDX can be used to profile the dynamics of the receptor in response to ligand binding[1]. Here we expand our work to include HDX of heterodimer/coactivator complexes in combination with cell-based and biochemical assays to identify the ligand induced coactivator specificity of NRs of interest.