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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gao, Xiang Xing, Lijuan Liu, Zhiwei Shi, Guangsen Qu, Zhipeng Ptácek, Louis J. Huang, Moli Wang, Xiaohan Liu, Yi Xu, Ying Wu, Xi Yan, Jie Dong, Zhen Yang, Ling |
| Description | Author Affiliation: Shi G ( Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Medical School of Nanjing University, Pukou District, Nanjing 210061, China.); |
| Abstract | The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erb , 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-erb 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-Erb :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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Circadian Rhythm Physiology Cryptochromes Metabolism F-Box Proteins Gene Expression Regulation Animals Genetics Gene Products, Rev Mice Mice, Knockout Response Elements Thyroid Hormone Receptors Alpha Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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