| First Author | Sun J | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 48 | Pages | 33118-24 |
| PubMed ID | 25324544 | Mgi Jnum | J:218800 |
| Mgi Id | MGI:5618399 | Doi | 10.1074/jbc.M114.610501 |
| Citation | Sun J, et al. (2014) beta-Apo-13-carotenone regulates retinoid X receptor transcriptional activity through tetramerization of the receptor. J Biol Chem 289(48):33118-24 |
| abstractText | Retinoid X receptor (RXRalpha) is activated by 9-cis-retinoic acid (9cRA) and regulates transcription as a homodimer or as a heterodimer with other nuclear receptors. We have previously demonstrated that beta-apo-13-carotenone, an eccentric cleavage product of beta-carotene, antagonizes the activation of RXRalpha by 9cRA in mammalian cells overexpressing this receptor. However, the molecular mechanism of beta-apo-13-carotenone's modulation on the transcriptional activity of RXRalpha is not understood and is the subject of this report. We performed transactivation assays using full-length RXRalpha and reporter gene constructs (RXRE-Luc) transfected into COS-7 cells, and luciferase activity was examined. beta-Apo-13-carotenone was compared with the RXRalpha antagonist UVI3003. The results showed that both beta-apo-13-carotenone and UVI3003 shifted the dose-dependent RXRalpha activation by 9cRA. In contrast, the results of assays using a hybrid Gal4-DBD:RXRalphaLBD receptor reporter cell assay that detects 9cRA-induced coactivator binding to the ligand binding domain demonstrated that UVI3003 significantly inhibited 9cRA-induced coactivator binding to RXRalphaLBD, but beta-apo-13-carotenone did not. However, both beta-apo-13-carotenone and UVI3003 inhibited 9-cRA induction of caspase 9 gene expression in the mammary carcinoma cell line MCF-7. To resolve this apparent contradiction, we investigated the effect of beta-apo-13-carotenone on the oligomeric state of purified recombinant RXRalphaLBD. beta-Apo-13-carotenone induces tetramerization of the RXRalphaLBD, although UVI3003 had no effect on the oligomeric state. These observations suggest that beta-apo-13-carotenone regulates RXRalpha transcriptional activity by inducing the formation of the "transcriptionally silent" RXRalpha tetramer. |
