title: p120 acts as a specific coactivator for 9-cis-retinoic acid receptor (RXR) on peroxisome proliferator-activated receptor-gamma/RXR heterodimers.
abstract: p120 was originally isolated as a novel nuclear co-activator for thyroid hormone receptor. In this study, we characterized its interaction and transactivation of peroxisome proliferator-activated receptor-gamma (PPARgamma) and 9-cis-retinoic acid receptor (RXR) heterodimers. Transient transfection study revealed that p120 enhanced the transcriptional activation of PPARgamma/RXR induced by PPARgamma- or RXR-specific ligands. In the glutathione-S-transferase pull-down assay, while steroid receptor coactivator-1 showed apparent interactions with both RXR and PPARgamma, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPARgamma even in the presence of thiazolidinediones. The yeast two-hybrid analysis showed no interaction of p120 with PPARgamma under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPARgamma/RXR/p120 complex formation only in the presence of 9-cis-RA. Furthermore, the yeast three-hybrid assay clearly revealed a significant interaction between p120 and PPARgamma via RXR of PPARgamma/RXR heterodimer only in the presence of 9-cis-RA. These findings indicate that p120 acts as a specific co-activator for the RXR of PPARgamma/RXR heterodimer in a 9-cis-RA-dependent manner.
authors.affiliation: First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan. tmonden@sb.gunma-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Monden
authors.forename: M
authors.initials: M
authors.lastname: Kishi
authors.forename: T
authors.initials: T
authors.lastname: Hosoya
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: F E
authors.initials: FE
authors.lastname: Wondisford
authors.forename: A N
authors.initials: AN
authors.lastname: Hollenberg
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014212:Tretinoin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000092468:Bromodomain Containing Proteins
chemical_list: D002352:Carrier Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D014212:Tretinoin; C099139:BRD8 protein, human; D000092468:Bromodomain Containing Proteins; C000607071:RARA protein, human; C000607072:Rara protein, mouse