| First Author | Dierickx P | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 25 | Pages | 12147-12152 |
| PubMed ID | 31127047 | Mgi Jnum | J:279241 |
| Mgi Id | MGI:6315432 | Doi | 10.1073/pnas.1904226116 |
| Citation | Dierickx P, et al. (2019) SR9009 has REV-ERB-independent effects on cell proliferation and metabolism. Proc Natl Acad Sci U S A 116(25):12147-12152 |
| abstractText | The nuclear receptors REV-ERBalpha and -beta link circadian rhythms and metabolism. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well as diseased animal models and cell systems. However, the direct involvement of REV-ERBs in these effects of SR9009 has not been thoroughly assessed, as experiments were not performed in the complete absence of both proteins. Here, we report the generation of a mouse model for conditional genetic deletion of REV-ERBalpha and -beta. We show that SR9009 can decrease cell viability, rewire cellular metabolism, and alter gene transcription in hepatocytes and embryonic stem cells lacking both REV-ERBalpha and -beta. Thus, the effects of SR9009 cannot be used solely as surrogate for REV-ERB activity. |
