RIP 140 enhances nuclear receptor-dependent transcription in vivo in yeast.
RIP140 has previously been cloned as a factor that interacts with the estrogen receptor (ER) in vitro. We demonstrate in this study that RIP140 is a co-factor 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.
Joyeux
A
A
INSERM U439, Montpellier, France.
Cavaillès
V
V
Balaguer
P
P
Nicolas
J C
JC
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005668:Furylfuramide / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D000072482:Retinoic Acid Receptor alpha; D005668:Furylfuramide; D004958:Estradiol; D014212:Tretinoin