Nuclear receptor coactivators: multiple enzymes, multiple complexes, multiple functions.

Abstract

Nuclear receptors are ligand-inducible transcription factors which mediate the physiological effects of steroid, thyroid and retinoid hormones. By regulating the assembly of a transcriptional preinitiation complex at the promoter of target genes, they enhance the expression of these genes in response to hormone. Recent evidence suggests that nuclear receptors act in part by recruiting multiple coregulator proteins which may have specific functions during transcriptional initiation. Liganded receptors recruit members of the SRC family, a group of structurally and functionally related transcriptional coactivators. Receptors also interact with the transcriptional cointegrators p300 and CBP, which are proposed to integrate diverse afferent signals at hormone-regulated promoters. p300/CBP and members of the SRC coactivator family have intrinsic histone acetyltransferase activity which is believed to disrupt the nucleosomal structure at these promoters. Other nuclear receptor coactivators include a member of the SWI/SNF complex, BRG-1, which couples ATP hydrolysis to chromatin remodelling, and the E3 ubiquitin-protein ligases E6-AP and RPF-1. Finally, nuclear receptor coactivators appear to be organized into preformed subcomplexes, an arrangement that may facilitate their efficient assembly into diverse higher order configurations.