ArticleCell cycle (Georgetown, Tex.)2009
A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation.
Article in Cell cycle (Georgetown, Tex.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Phosphorylation and Circadian Molecular Timing.Frontiers in physiology · 2020Pooled it
- Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms.Medicinal research reviews · 2026Review
- CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators.Nature cell biology · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TOC1 phosphorylation disproportionally enhances chromatin binding at rhythmic gene promoters.Science advances · 2025Article
- O-GlcNAcylation of nuclear proteins in the mouse liver exhibit daily oscillations that are influenced by meal timing.PLoS biology · 2025Article
- Mealtime alters daily rhythm in nuclear O-GlcNAc proteome to regulate hepatic gene expression.bioRxiv : the preprint server for biology · 2025Article
- Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling.Genes & development · 2024Article
- Circadian rhythm disruption and endocrine-related tumors.World journal of clinical oncology · 2024Review
- Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.Cellular and molecular neurobiology · 2024Article
- Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.Aging and disease · 2024Review
- Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- A Complex Relationship Among the Circadian Rhythm, Reward Circuit and Substance Use Disorder (SUD).Psychology research and behavior management · 2024Review
- Watching the clock in glioblastoma.Neuro-oncology · 2023Review
- Mood phenotypes in rodent models with circadian disturbances.Neurobiology of sleep and circadian rhythms · 2022Review
- Input integration by the circadian clock exhibits nonadditivity and fold-change detection.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Complex physiology and clinical implications of time-restricted eating.Physiological reviews · 2022Review
- The impact of lithium on circadian rhythms and implications for bipolar disorder pharmacotherapy.Neuroscience letters · 2022Review
- Magnetic field effects in biology from the perspective of the radical pair mechanism.Journal of the Royal Society, Interface · 2022Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The circadian clock regulates biological processes from gene expression to organism behavior in a precise, sustained rhythm that is generated at the unicellular level by coordinated function of interlocked transcriptional feedback loops and post-translational modifications of core clock proteins. CLOCK phosphorylation regulates transcriptional activity, cellular localization and stability; however little is known about the specific residues and enzymes involved. We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427. Mutational analysis and protein stability assays indicate that this serine cluster functions as a phospho-degron. Through the use of GSK-3 activators/inhibitors and kinase assays, we demonstrate that GSK-3beta regulates the degron site by increasing CLOCK phosphorylation/degradation, which correlates with an increase in the expression of CLOCK responsive promoters. Stabilization of phospho-deficient CLOCK delays the phase of oscillation in synchronized fibroblasts. This investigation begins the characterization of a complex phospho-regulatory site that controls the activity and degradation of CLOCK, a core transcription factor that is essential for circadian behavior.
Indexed as
Identifiers
What OpenQuestion holds
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.