ArticleMolecular cell2023
PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms.Medicinal research reviews · 2026Review
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.eLife · 2026Article
- Article
- Gut microbiome-produced bile acid metabolite lengthens the circadian period in host intestinal cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- The mitotic functions of a fission yeast CK1 enzyme are regulated by Cdk1-dependent and auto-phosphorylation.The Journal of biological chemistry · 2026Article
- Markovian state models uncover casein kinase 1 dynamics that govern circadian period.Biophysical journal · 2025Article
- Old cogs, new clocks: a conserved protein complex controls developmental and circadian timing.The EMBO journal · 2025Article
- A conserved chronobiological complex times C. elegans development.The EMBO journal · 2025Article
- ProteinsPlus: a publicly available resource for protein structure mining.Nucleic acids research · 2025Article
- A wrinkle in timers: evolutionary rewiring of conserved biological timekeepers.Trends in biochemical sciences · 2025Review
- Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock.Biomedicines · 2025Review
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Unveiling the role of melatonin-related gene CSNK1D in osteoclastogenesis and its implications for osteoporosis treatment.Experimental physiology · 2025Article
- PERspectives on circadian cell biology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Research progress on the role and mechanism of circadian clock geneFrontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
PERIOD (PER) and Casein Kinase 1δ regulate circadian rhythms through a phosphoswitch that controls PER stability and repressive activity in the molecular clock. CK1δ phosphorylation of the familial advanced sleep phase (FASP) serine cluster embedded within the Casein Kinase 1 binding domain (CK1BD) of mammalian PER1/2 inhibits its activity on phosphodegrons to stabilize PER and extend circadian period. Here, we show that the phosphorylated FASP region (pFASP) of PER2 directly interacts with and inhibits CK1δ. Co-crystal structures in conjunction with molecular dynamics simulations reveal how pFASP phosphoserines dock into conserved anion binding sites near the active site of CK1δ. Limiting phosphorylation of the FASP serine cluster reduces product inhibition, decreasing PER2 stability and shortening circadian period in human cells. We found that Drosophila PER also regulates CK1δ via feedback inhibition through the phosphorylated PER-Short domain, revealing a conserved mechanism by which PER phosphorylation near the CK1BD regulates CK1 kinase activity.
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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.