Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity Evidence for a Potential Role for RIP140 英文参考文献.docVIP

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Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity Evidence for a Potential Role for RIP140 英文参考文献.doc

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Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity Evidence for a Potential Role for RIP140 英文参考文献

RetinoicAcidMediatesLong-PacedOscillationsin RetinoidReceptorActivity:EvidenceforaPotentialRole forRIP140 KellyC.Heim1.,JoshuaJ.Gamsby2.,MaryP.Hever1,SarahJ.Freemantle1,JenniferJ.Loros2,JayC. Dunlap2,MichaelJ.Spinella1,3* 1DepartmentofPharmacologyandToxicology,Hanover,NewHampshire,UnitedStatesofAmerica,2DepartmentofGenetics,DartmouthMedicalSchool,Hanover,New Hampshire,UnitedStatesofAmerica,3NorrisCottonCancerCenter,DartmouthHitchcockMedicalCenter,Hanover,NewHampshire,UnitedStatesofAmerica Abstract Background: Mechanisms that underlie oscillatory transcriptional activity of nuclear receptors (NRs) are incompletely understood.Evidenceexistsforrapid,cyclicrecruitmentofcoregulatorycomplexesuponactivationofnuclearreceptors. RIP140isaNRcoregulatorthatrepressesthetransactivationofagonist-bound nuclearreceptors.Previously,weshowed that RIP140 is inducible by all-trans retinoic acid (RA) and mediates limiting, negative-feedback regulation of retinoid signaling. MethodologyandFindings:HerewereportthatinthecontinuedpresenceofRA,long-pacedoscillationsofretinoicacid receptor(RAR)activityoccurwithaperiodrangingfrom24to35hours.EndogenousexpressionofRIP140andotherRA- target genes also oscillate in the presence of RA. Cyclic retinoid receptor transactivation is ablated by constitutive overexpressionofRIP140.Further,depletionofRIP140disruptscyclicexpressionoftheRAtargetgeneHOXA5.Evidenceis provided that RIP140 may limit RAR signaling in a selective, non-redundant manner in contrast to the classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle, and may be partially redundant in limiting RAR activity.Finally,evidenceisprovidedthatRIP140canrepressandbeinducedbyothernuclearreceptorsinamannerthat suggestspotentialparticipationinotherNRoscillations. Conclusions and Significance: We provide evidence for novel, long-paced oscillatory retinoid receptor activity and hypothesize that this may be paced in part, by RIP140. Oscillatory NR activity may be involved in