Monden T, Kishi M, Hosoya T, Satoh T, Wondisford F E, Hollenberg A N, Yamada M, Mori M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Mol Endocrinol. 1999 Oct;13(10):1695-703. doi: 10.1210/mend.13.10.0353.
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.
p120最初作为一种新型的甲状腺激素受体核共激活因子被分离出来。在本研究中，我们对其与过氧化物酶体增殖物激活受体γ（PPARγ）和9-顺式视黄酸受体（RXR）异二聚体的相互作用及反式激活作用进行了表征。瞬时转染研究表明，p120增强了由PPARγ或RXR特异性配体诱导的PPARγ/RXR的转录激活。在谷胱甘肽-S-转移酶下拉实验中，虽然类固醇受体共激活因子-1与RXR和PPARγ均表现出明显的相互作用，但p120仅以9-顺式视黄酸（RA）依赖的方式与RXR结合，即使在噻唑烷二酮存在的情况下也不与PPARγ结合。酵母双杂交分析表明，在任何条件下p120与PPARγ均无相互作用，电泳迁移率变动分析表明，仅在9-顺式RA存在时才出现明显的DNA-PPARγ/RXR/p120复合物形成。此外，酵母三杂交分析清楚地表明，仅在9-顺式RA存在时，p120通过PPARγ/RXR异二聚体的RXR与PPARγ之间存在显著的相互作用。这些发现表明，p120以9-顺式RA依赖的方式作为PPARγ/RXR异二聚体中RXR的特异性共激活因子。
