| First Author | Busino L | Year | 2007 |
| Journal | Science | Volume | 316 |
| Issue | 5826 | Pages | 900-4 |
| PubMed ID | 17463251 | Mgi Jnum | J:121579 |
| Mgi Id | MGI:3710695 | Doi | 10.1126/science.1141194 |
| Citation | Busino L, et al. (2007) SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science 316(5826):900-4 |
| abstractText | One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins. |
