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

Nuclear receptors are ligand-inducible transcription factors which mediate the physiological effects of steroid, thyroid and retinoid hormones. By reg ulating the assembly of a transcriptional preinitiation complex at the prom oter of target genes, they enhance the expression of these genes in respons e to hormone. Recent evidence suggests that nuclear receptors act in part b y recruiting multiple coregulator proteins which may have specific function s during transcriptional initiation. Liganded receptors recruit members of the SRC family, a group of structurally and functionally related transcript ional coactivators. Receptors also interact with the transcriptional cointe grators p300 and CBP, which are proposed to integrate diverse afferent sign als at hormone-regulated promoters. p300/CBP and members of the SRC coactiv ator family have intrinsic histone acetyltransferase activity which is beli eved to disrupt the nucleosomal structure at these promoters. Other nuclear receptor coactivators include a member of the SWI/SNF complex, BRG-1, whic h couples ATP hydrolysis to chromatin remodelling, and the E3 ubiquitin-pro tein ligases E6-AP and RPF-1. Finally, nuclear receptor coactivators appear to be organized into preformed subcomplexes, an arrangement that may facil itate their efficient assembly into diverse higher order configurations. (C ) 1999 Elsevier Science Ltd. All rights reserved.