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-γ (PPARγ) and 9-cis-retinoic acid receptor (RXR) heterodimers. Transient transfection study revealed that p120 enhanced the transcriptional activation of PPARγ/RXR induced by PPARγ- 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 PPARγ, p120 bound only to RXR in a 9-cis-retinoic acid (RA)-dependent manner and also did not bind to PPARγ even in the presence of thiazolidinediones. The yeast two-hybrid analysis showed no interaction of p120 with PPARγ under any conditions, and electophoretic mobility shift assay showed apparent DNA-PPARγ/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 PPARγ via RXR of PPARγ/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 PPARγ/RXR heterodimer in a 9-cis-RA-dependent manner.
ASJC Scopus subject areas
- Molecular Biology