| First Author | Shi G | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 12 | Pages | 4750-5 |
| PubMed ID | 23471982 | Mgi Jnum | J:194250 |
| Mgi Id | MGI:5471867 | Doi | 10.1073/pnas.1302560110 |
| Citation | Shi G, et al. (2013) Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock. Proc Natl Acad Sci U S A 110(12):4750-5 |
| abstractText | The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erbalpha, a member of the nuclear receptor family, is an essential component of the interlocking loop. To understand the roles of different clock genes, we conducted a genetic interaction screen by generating single- and double-mutant mice. We found that the deletion of Rev-erbalpha in F-box/leucine rich-repeat protein (Fbxl3)-deficient mice rescued its long-circadian period phenotype, and our results further revealed that FBXL3 regulates Rev-Erb/retinoic acid receptor-related orphan receptor-binding element (RRE)-mediated transcription by inactivating the Rev-Erbalpha:histone deacetylase 3 corepressor complex. By analyzing the Fbxl3 and Cryptochrome 1 double-mutant mice, we found that FBXL3 also regulates the amplitudes of E-box-driven gene expression. These two separate roles of FBXL3 in circadian feedback loops provide a mechanism that contributes to the period determination and robustness of the clock. |
