ArticleThe Journal of biological chemistry2009
Sequential and compartment-specific phosphorylation controls the life cycle of the circadian CLOCK protein.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Evolution of canonical circadian clock genes underlies unique sleep strategies of marine mammals for secondary aquatic adaptation.PLoS genetics · 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
- Systematic analysis of the impact of phosphorylation and O-GlcNAcylation on protein subcellular localization.Cell reports · 2023Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- It's about time: Analysing simplifying assumptions for modelling multi-step pathways in systems biology.PLoS computational biology · 2020Article
- Review
- The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila.PLoS genetics · 2015Article
- The molecular ticks of the Drosophila circadian clock.Current opinion in insect science · 2015Article
- Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila.The Journal of biological chemistry · 2014Article
- A neuropeptide speeds circadian entrainment by reducing intercellular synchrony.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator.PLoS biology · 2013Article
- EARLY FLOWERING4 recruitment of EARLY FLOWERING3 in the nucleus sustains the Arabidopsis circadian clock.The Plant cell · 2012Article
- The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.EMBO reports · 2011Article
- Of switches and hourglasses: regulation of subcellular traffic in circadian clocks by phosphorylation.EMBO reports · 2010Article
- A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation.Cell cycle (Georgetown, Tex.) · 2009Article
- Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale.Genes & development · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The circadian clock facilitates a temporal coordination of most homeostatic activities and their synchronization with the environmental cycles of day and night. The core oscillating activity of the circadian clock is formed by a heterodimer of the transcription factors CLOCK (CLK) and CYCLE (CYC). Post-translational regulation of CLK/CYC has previously been shown to be crucial for clock function and accurate timing of circadian transcription. Here we report that a sequential and compartment-specific phosphorylation of the Drosophila CLK protein assigns specific localization and activity patterns. Total and nuclear amounts of CLK protein were found to oscillate over the course of a day in circadian neurons. Detailed analysis of the cellular distribution and phosphorylation of CLK revealed that newly synthesized CLK is hypophosphorylated in the cytoplasm prior to nuclear import. In the nucleus, CLK is converted into an intermediate phosphorylation state that correlates with trans-activation of circadian transcription. Hyperphosphorylation and degradation are promoted by nuclear export of the CLK protein. Surprisingly, CLK localized to discrete nuclear foci in cell culture as well as in circadian neurons of the larval brain. These subnuclear sites likely contain a storage form of the transcription factor, while homogeneously distributed nuclear CLK appears to be the transcriptionally active form. These results show that sequential post-translational modifications and subcellular distribution regulate the activity of the CLK protein, indicating a core post-translational timing mechanism of the circadian clock.
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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.