ArticleProceedings of the National Academy of Sciences of the United States of America2014
Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Identification of circadian rhythm-associated key genes in metabolic dysfunction-associated fatty liver disease.Clinical and experimental medicine · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- CRY1 Lysine 151 Regulates Circadian Rhythms Through Ubiquitination-Independent Protein Interactions.International journal of molecular sciences · 2025Article
- Pharmacokinetic Model-Based Control across the Blood-Brain Barrier for Circadian Entrainment.International journal of molecular sciences · 2023Article
- Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets.Cancer metastasis reviews · 2023Review
- Transcription Repression of CRY2 via PER2 Interaction Promotes Adipogenesis.Molecular and cellular biology · 2023Article
- Limits of entrainment of circadian neuronal networks.Chaos (Woodbury, N.Y.) · 2023Article
- Exploring the prevalence and burden of sleep disturbance in primary brain tumor patients.Neuro-oncology practice · 2022Article
- Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1.International journal of oral science · 2022Article
- Nutrient timing and metabolic regulation.The Journal of physiology · 2022Review
- Cell-Based Phenotypic Screens to Discover Circadian Clock-Modulating Compounds.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
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- Enhanced Understanding of Molecular Interactions and Function Underlying Pain Processes Through Networks of Transcript Isoforms, Genes, and Gene Families.Advances and applications in bioinformatics and chemistry : AABC · 2021Article
- Circadian zinc feeding regime in laying hens related to laying performance, oxidation status, and interaction of zinc and calcium.Poultry science · 2020Article
- Astrocytic Modulation of Neuronal Activity in the Suprachiasmatic Nucleus: Insights from Mathematical Modeling.Journal of biological rhythms · 2020Article
- Orchestration of Circadian Timing by Macromolecular Protein Assemblies.Journal of molecular biology · 2020Review
- Calcium Sets the Clock in Ameloblasts.Frontiers in physiology · 2020Article
- Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling.The European journal of neuroscience · 2020Article
- Mathematical modeling of circadian rhythms.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Posttranslational regulation of clock proteins is an essential part of mammalian circadian rhythms, conferring sensitivity to metabolic state and offering promising targets for pharmacological control. Two such regulators, casein kinase 1 (CKI) and F-box and leucine-rich repeat protein 3 (FBXL3), modulate the stability of closely linked core clock proteins period (PER) and cryptochrome (CRY), respectively. Inhibition of either CKI or FBXL3 leads to longer periods, and their effects are independent despite targeting proteins with similar roles in clock function. A mechanistic understanding of this independence, however, has remained elusive. Our analysis of cellular circadian clock gene reporters further differentiated between the actions of CKI and FBXL3 by revealing opposite amplitude responses from each manipulation. To understand the functional relationship between the CKI-PER and FBXL3-CRY pathways, we generated robust mechanistic predictions by applying a bootstrap uncertainty analysis to multiple mathematical circadian models. Our results indicate that CKI primarily regulates the accumulating phase of the PER-CRY repressive complex by controlling the nuclear import rate, whereas FBXL3 separately regulates the duration of transcriptional repression in the nucleus. Dynamic simulations confirmed that this spatiotemporal separation is able to reproduce the independence of the two regulators in period regulation, as well as their opposite amplitude effect. As a result, this study provides further insight into the molecular clock machinery responsible for maintaining robust circadian rhythms.
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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.