| First Author | Okabe T | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 21 | Pages | 4143-4154 |
| PubMed ID | 27686098 | Mgi Jnum | J:247279 |
| Mgi Id | MGI:5922302 | Doi | 10.1242/jcs.190959 |
| Citation | Okabe T, et al. (2016) REV-ERBalpha influences the stability and nuclear localization of the glucocorticoid receptor. J Cell Sci 129(21):4143-4154 |
| abstractText | REV-ERBalpha (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBalpha binds to the C-terminal portion and GR to the N-terminal portion of HSP90alpha and HSP90beta, a chaperone responsible for the activation of proteins to ensure survival of a cell. The presence of REV-ERBalpha influences the stability and nuclear localization of GR by an unknown mechanism, thereby affecting expression of GR target genes, such as IkappaBalpha (Nfkbia) and alcohol dehydrogenase 1 (Adh1). Our findings highlight an important interplay between two nuclear receptors that influence the transcriptional potential of each other. This indicates that the transcriptional landscape is strongly dependent on dynamic processes at the protein level. |
