RIP-140 ENHANCES NUCLEAR RECEPTOR-DEPENDENT TRANSCRIPTION IN-VIVO IN YEAST

RIP140 has previoulsy been cloned as a factor that interacts with the estrogen receptor (ER) in vitro. We demonstrate in this study that RIP 140 is a cofactor for nuclear receptor in yeast. RIP140 enhances the E R transcriptional activity by increasing 1.5- to 4-fold the induction factor of the reporter gene response at saturating hormone concentrati ons, this effect being magnified at suboptimal doses of estradiol. Mor eover, RIP140 decreases the ED(50) of the dose-response curve. These e ffects are recovered with an N-terminal truncated ER, but impaired by point mutations that abolish AFP-AD activity. We did not observe any m odulation of the partial agonist 4-hydroxytamoxifen activity in the pr esence of RIP140, Thus, RIP140 modulates transcriptional activity of E R through the AFP-AD domain and in a agonist-dependent fashion. RIP140 is also a strong coactivator for the retinoid pathway, as its express ion enhances 10-fold the transactivation of a chimeric retinoic acid-a lpha receptor at saturant hormone concentration and left shifted 5-fol d the ED(50) of the dose-response curve. We have investigated whether RIP140 could be involved in cross-talk between estrogenic and retinoid pathways.