RIP-140 INTERACTS WITH MULTIPLE NUCLEAR RECEPTORS BY MEANS OF 2 DISTINCT SITES

We have characterized two distinct binding sites, called site 1 and si te 2, in the nuclear protein RIP-140 which interact with the ligand bi nding domain of the estrogen receptor both in solution and when the re ceptor is bound to DNA, Both sites are capable of independently intera cting with other nuclear receptors, including the thyroid hormone and retinoic acid receptors, but they are not identical since the interact ion with retinoid X receptor is mediated primarily by site 1. The inte raction is enhanced by agonists but not by antagonists, and the in vit ro binding activities to a number of mutant receptors correlate with t heir abilities to stimulate transcription in vivo. When RIP-140 is fus ed to heterologous DNA binding domains, it is able to stimulate the tr anscription of reporter genes in both yeast and mammalian cells. Thus, RIP-140 is likely to function as a bridging protein between receptors and the basal transcription machinery and thereby stimulate the trans cription of target genes.