| First Author | Huppunen J | Year | 2004 |
| Journal | Mol Cell Endocrinol | Volume | 219 |
| Issue | 1-2 | Pages | 151-60 |
| PubMed ID | 15149736 | Mgi Jnum | J:210925 |
| Mgi Id | MGI:5572884 | Doi | 10.1016/j.mce.2004.01.002 |
| Citation | Huppunen J, et al. (2004) Requirements for transcriptional regulation by the orphan nuclear receptor ERRgamma. Mol Cell Endocrinol 219(1-2):151-60 |
| abstractText | Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor lacking identified natural ligands. We have addressed the requirements for ERRgamma-mediated gene regulation. ERRgamma transactivates constitutively reporter genes driven by ERR response elements (ERREs) or estrogen response elements (EREs). The activation depends on an intact DNA-binding domain (DBD) and activation function-2 (AF2). ERRgamma-mediated transactivation is further enhanced by peroxisome proliferator-activated receptor coactivator-1. Interestingly, ligand-binding domain (LBD) mutations predicted to either enlarge or diminish the putative ligand-binding pocket have no effect on the transcriptional activity implying that ERRgamma activity does not depend on any ligands. Antiestrogens 4OH-tamoxifen (4OHT) and 4-hydroxytoremifene (4OHtor) inhibit the ability of ERR to transactivate ERRE and ERE reporters. In contrast, ERRgamma activates transcription at AP-1 sites in the presence of 4OHT and 4OHtor. Thus, the transcriptional activity of ERRgamma seems not to require ligand binding but is modulated by binding of certain small synthetic ligands. |
