ArticleGenes & development2008
The phospho-occupancy of an atypical SLIMB-binding site on PERIOD that is phosphorylated by DOUBLETIME controls the pace of the clock.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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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
100 citing papers in PubMed.
- Article
- Oligomerization of PER2 as a dynamic mode of regulation of the mammalian circadian clock.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
- Article
- A wrinkle in timers: evolutionary rewiring of conserved biological timekeepers.Trends in biochemical sciences · 2025Review
- A Compensated Clock: Temperature and Nutritional Compensation Mechanisms Across Circadian Systems.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Drosophila ubiquitin-specific peptidase 14 stabilizes the PERIOD protein by regulating a ubiquitin ligase SLIMB.Communications biology · 2025Article
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans.Scientific reports · 2024Article
- Alternative splicing ofbioRxiv : the preprint server for biology · 2024Article
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- PERIOD phosphorylation leads to feedback inhibition of CK1 activity to control circadian period.Molecular cell · 2023Article
- Seasonal cues act through the circadian clock and pigment-dispersing factor to control EYES ABSENT and downstream physiological changes.Current biology : CB · 2023Article
- Functional analysis of 110 phosphorylation sites on the circadian clock protein FRQ identifies clusters determining period length and temperature compensation.G3 (Bethesda, Md.) · 2023Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- Article
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022Review
40 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
A common feature of animal circadian clocks is the progressive phosphorylation of PERIOD (PER) proteins, which is highly dependent on casein kinase Idelta/epsilon (CKIdelta/epsilon; termed DOUBLETIME [DBT] in Drosophila) and ultimately leads to the rapid degradation of hyperphosphorylated isoforms via a mechanism involving the F-box protein, beta-TrCP (SLIMB in Drosophila). Here we use the Drosophila melanogaster model system, and show that a key step in controlling the speed of the clock is phosphorylation of an N-terminal Ser (S47) by DBT, which collaborates with other nearby phosphorylated residues to generate a high-affinity atypical SLIMB-binding site on PER. DBT-dependent increases in the phospho-occupancy of S47 are temporally gated, dependent on the centrally located DBT docking site on PER and partially counterbalanced by protein phosphatase activity. We propose that the gradual DBT-mediated phosphorylation of a nonconsensus SLIMB-binding site establishes a temporal threshold for when in a daily cycle the majority of PER proteins are tagged for rapid degradation. Surprisingly, most of the hyperphosphorylation is unrelated to direct effects on PER stability. We also use mass spectrometry to map phosphorylation sites on PER, leading to the identification of a number of "phospho-clusters" that explain several of the classic per mutants.
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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.