title: Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.
abstract: Receptor interacting protein 140 (RIP140) interacts with retinoic acid receptor (RAR) and retinoid X receptor (RXR) constitutively, but hormone binding enhances this interaction. The ligand-independent interaction is mediated by the amino and central regions of RIP140 which contain a total of nine copies of the LXXLL motif, whereas the agonist-induced interaction is mediated by its carboxyl terminus which contains a novel motif (1063-1076, LTKTNPILYYMLQK). The ligand-independent interaction could be enhanced slightly by agonists, whereas the ligand-dependent interaction was strictly agonist dependent for both RAR and RXR. In the context of heterodimers, ligand occupancy of RXR played a more dominant role for both molecular interaction and biological activity of RIP140. Competition and mutation studies demonstrated an essential role for (1067)Asn and (1073)Met for a ligand-dependent interaction. A model was proposed to address the constitutive and agonist-dependent interaction of RIP140 with RAR/RXR.
authors.affiliation: Department of Pharmacology and Biochemistry, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: Farooqui
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Franco
authors.forename: Jim
authors.initials: J
authors.lastname: Thompson
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kagechika
authors.forename: Roshantha A S
authors.initials: RA
authors.lastname: Chandraratna
authors.forename: Len
authors.initials: L
authors.lastname: Banaszak
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D008024:Ligands; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000078723:Nuclear Receptor Interacting Protein 1; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008024:Ligands; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D010446:Peptide Fragments; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors