ArticleThe Journal of biological chemistry2014
Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Tissue-specific CLOCK isoforms modulate circadian feedback loops to govern reproductive fitness in Drosophila.Cellular and molecular life sciences : CMLS · 2025Article
- Alternative splicing ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alternative splicing ofbioRxiv : the preprint server for biology · 2024Article
- Article
- Inhibition of Expression of the Circadian Clock GeneInternational journal of molecular sciences · 2023Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- CRUMB: a shiny-based app to analyze rhythmic feeding inF1000Research · 2023Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- Molecular mechanism of the repressive phase of the mammalian circadian clock.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Proteomic analysis of Drosophila CLOCK complexes identifies rhythmic interactions with SAGA and Tip60 complex component NIPPED-A.Scientific reports · 2020Article
- Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance.PLoS genetics · 2019Article
- CLOCK stabilizes CYCLE to initiate clock function inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging.Nature communications · 2017Article
- RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides.PLoS genetics · 2017Article
- Cycles of circadian illuminance are sufficient to entrain and maintain circadian locomotor rhythms in Drosophila.Scientific reports · 2016Article
- CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE.PLoS genetics · 2016Article
- Pacemaker-neuron-dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis.G3 (Bethesda, Md.) · 2016Article
- Evolutionary divergence of core and post-translational circadian clock genes in the pitcher-plant mosquito, Wyeomyia smithii.BMC genomics · 2015Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Circadian (≅ 24 h) clocks control daily rhythms in metabolism, physiology, and behavior in animals, plants, and microbes. In Drosophila, these clocks keep circadian time via transcriptional feedback loops in which clock-cycle (CLK-CYC) initiates transcription of period (per) and timeless (tim), accumulating levels of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key events in this feedback loop are controlled by, or coincide with, rhythms in PER and CLK phosphorylation, where PER and CLK phosphorylation is high during transcriptional repression. PER phosphorylation at specific sites controls its subcellular localization, activity, and stability, but comparatively little is known about the identity and function of CLK phosphorylation sites. Here we identify eight CLK phosphorylation sites via mass spectrometry and determine how phosphorylation at these sites impacts behavioral and molecular rhythms by transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four of these sites accelerates the feedback loop to shorten the circadian period, whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby increasing PER levels and accelerating transcriptional repression. These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop.
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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.