ArticleProceedings of the National Academy of Sciences of the United States of America2013
Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Phosphorylation of FBXL3 mediates GLDC polyubiquitination to suppress MHC-I expression and promote cancer immune evasion.Cell insight · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Disrupted diencephalon development and neuropeptidergic pathways in zebrafish with autism-risk mutations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- Linear poly-ubiquitin remodels the proteome and influences hundreds of regulators in Drosophila.G3 (Bethesda, Md.) · 2024Article
- Circadian period is compensated for repressor protein turnover rates in single cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mood phenotypes in rodent models with circadian disturbances.Neurobiology of sleep and circadian rhythms · 2022Review
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- Decoupling PER phosphorylation, stability and rhythmic expression from circadian clock function by abolishing PER-CK1 interaction.Nature communications · 2022Article
- Cell-cell coupling and DNA methylation abnormal phenotypes in the after-hours mice.Epigenetics & chromatin · 2021Article
- Introduction to the Clock System.Advances in experimental medicine and biology · 2021Article
- High-throughput discovery of genetic determinants of circadian misalignment.PLoS genetics · 2020Article
- Calcium Sets the Clock in Ameloblasts.Frontiers in physiology · 2020Article
- Phenotypic proteomic profiling identifies a landscape of targets for circadian clock-modulating compounds.Life science alliance · 2019Article
- SIRT7 couples light-driven body temperature cues to hepatic circadian phase coherence and gluconeogenesis.Nature metabolism · 2019Article
- The intricate dance of post-translational modifications in the rhythm of life.Nature structural & molecular biology · 2016Review
- Focused screening of mitochondrial metabolism reveals a crucial role for a tumor suppressor Hbp1 in ovarian reserve.Cell death and differentiation · 2016Article
- Circadian Oscillators: Around the Transcription-Translation Feedback Loop and on to Output.Trends in biochemical sciences · 2016Review
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erbα, 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-erbα 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-Erbα: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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.