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Molecular Endocrinology 11 (2): 193-202
Copyright © 1997 by The Endocrine Society

RIP 140 Enhances Nuclear Receptor-Dependent Transcription in Vivo in Yeast

A. Joyeux, V. Cavaillès, P. Balaguer and J. C. Nicolas

INSERM U439 (A.J., P.B., J.C.N.) and INSERM U148 (V.C.), 34090 Montpellier, France

RIP140 has previoulsy been cloned as a factor that interacts with the estrogen receptor (ER) in vitro. We demonstrate in this study that RIP140 is a cofactor for nuclear receptor in yeast. RIP140 enhances the ER transcriptional activity by increasing 1.5- to 4-fold the induction factor of the reporter gene response at saturating hormone concentrations, this effect being magnified at suboptimal doses of estradiol. Moreover, RIP140 decreases the ED50 of the dose-response curve. These effects are recovered with an N-terminal truncated ER, but impaired by point mutations that abolish AF2-AD activity. We did not observe any modulation of the partial agonist 4-hydroxytamoxifen activity in the presence of RIP140. Thus, RIP140 modulates transcriptional activity of ER through the AF2-AD domain and in a agonist-dependent fashion. RIP140 is also a strong coactivator for the retinoid pathway, as its expression enhances 10-fold the transactivation of a chimeric retinoic acid-{alpha} receptor at saturant hormone concentration and left shifted 5-fold the ED50 of the dose-response curve. We have investigated whether RIP140 could be involved in cross-talk between estrogenic and retinoid pathways.




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