p120 acts as a specific coactivator for 9-cis-retinoic acid receptor (RXR)on peroxisome proliferator-activated receptor-gamma/RXR heterodimers

p120 was originally isolated as a novel nuclear coactivator for thyroid hor mone receptor. In this study, we characterized its interaction and transact ivation of peroxisome proliferator-activated receptor-gamma (PPAR gamma) an d 9-cis-retinoic acid receptor (RXR) heterodimers. Transient transfection s tudy revealed that p120 enhanced the transcriptional activation of PPAR gam ma/RXR induced by PPAR gamma- or RXR-specific ligands. In the glutathione-S -transferase pull-down assay, while steroid receptor co-activator-1 showed apparent interactions with both RXR and PPAR gamma, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPA R gamma even in the presence of thiazolidinediones, The yeast two-hybrid an alysis showed no interaction of p120 with FFAR gamma under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPAR gamma/RXR/ p120 complex formation only in the presence of 9-cis-RA. Furthermore, the y east three-hybrid assay clearly revealed a significant interaction between p120 and PPAR gamma via RXR of PPAR gamma/RXR heterodimer only in the prese nce of 9-cis-RA, These findings indicate that p120 acts as a specific coact ivator for the RXR of PPAR gamma/RXR heterodimer in a 9-cis-RA-dependent ma nner.