ArticleProceedings of the National Academy of Sciences of the United States of America2009
Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Phosphorylation and Circadian Molecular Timing.Frontiers in physiology · 2020Pooled it
- Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms.Medicinal research reviews · 2026Review
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Review
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Interplay between circadian rhythms, gut microbiota, and MASLD: from mechanistic foundations to therapeutic opportunities.Frontiers in medicine · 2026Review
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development.Cell communication and signaling : CCS · 2025Review
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein kinase 1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein Kinase 1.bioRxiv : the preprint server for biology · 2024Article
- Circadian rhythm disruption and endocrine-related tumors.World journal of clinical oncology · 2024Review
- The Dawn and Advancement of the Knowledge of the Genetics of Migraine.Journal of clinical medicine · 2024Review
- Metabolic and chemical architecture of the mammalian circadian clock.Cell chemical biology · 2023Review
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping.iScience · 2023Article
- Circadian Responses to Light in the BTBR Mouse.Journal of biological rhythms · 2022Article
- Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression.International journal of molecular sciences · 2022Article
- Kinase domain autophosphorylation rewires the activity and substrate specificity of CK1 enzymes.Molecular cell · 2022Article
- Casein kinase 1 and disordered clock proteins form functionally equivalent, phospho-based circadian modules in fungi and mammals.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Implementing a Scoring Function Based on Interaction Fingerprint for Autogrow4: Protein Kinase CK1δ as a Case Study.Frontiers in molecular biosciences · 2022Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Circadian rhythms in mammals are generated by a negative transcriptional feedback loop in which PERIOD (PER) is rate-limiting for feedback inhibition. Casein kinases Idelta and Iepsilon (CKIdelta/epsilon) can regulate temporal abundance/activity of PER by phosphorylation-mediated degradation and cellular localization. Despite their potentially crucial effects on PER, it has not been demonstrated in a mammalian system that these kinases play essential roles in circadian rhythm generation as does their homolog in Drosophila. To disrupt both CKIdelta/epsilon while avoiding the embryonic lethality of CKIdelta disruption in mice, we used CKIdelta-deficient Per2(Luc) mouse embryonic fibroblasts (MEFs) and overexpressed a dominant-negative mutant CKIepsilon (DN-CKIepsilon) in the mutant MEFs. CKIdelta-deficient MEFs exhibited a robust circadian rhythm, albeit with a longer period, suggesting that the cells possess a way to compensate for CKIdelta loss. When CKIepsilon activity was disrupted by the DN-CKIepsilon in the mutant MEFs, circadian bioluminescence rhythms were eliminated and rhythms in endogenous PER abundance and phosphorylation were severely compromised, demonstrating that CKIdelta/epsilon are indeed essential kinases for the clockwork. This is further supported by abolition of circadian rhythms when physical interaction between PER and CKIdelta/epsilon was disrupted by overexpressing the CKIdelta/epsilon binding domain of PER2 (CKBD-P2). Interestingly, CKBD-P2 overexpression led to dramatically low levels of endogenous PER, while PER-binding, kinase-inactive DN-CKIepsilon did not, suggesting that CKIdelta/epsilon may have a non-catalytic role in stabilizing PER. Our results show that an essential role of CKIdelta/epsilon is conserved between Drosophila and mammals, but CKIdelta/epsilon and DBT may have divergent non-catalytic functions in the clockwork as well.
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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.