Nuclear receptor coactivators and corepressors

The nuclear receptors belong to a superfamily of proteins, many of which are ligand-regulated, that bind to specific DNA sequences and control specific gene transcription. Recent data show that, in addition to contacting the basal transcription machinery directly, nuclear receptors inhibit or enhance transcription by recruiting an array of coactivator or corepressor proteins to the transcription complex. In this review we define the properties of these putative coregulatory factors; we describe the basal and coregulatory factors that are currently known to interact with nuclear receptors; we suggest various mechanisms by which coactivators and corepressors act; we discuss issues that are raised by the presence of multiple, perhaps competing, coregulatory factors; and we speculate how these additional regulatory layers may explain the heterogeneity of hormone responses that are observed in normal and malignant tissues.