ArticleGenes & development2012
CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- NDRG2 orchestrates circadian clock stability to suppress tumorigenesis and potentiate oxaliplatin response in colorectal cancer.Oncogene · 2026Article
- Deubiquitinase USP8 regulates the spindle assembly checkpoint in oocytes.Science advances · 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
- Elucidation of short linear motif-based interactions of the MIT and rhodanese domains of the ubiquitin-specific protease 8.Biology direct · 2025Article
- Photoneuroendocrine, circadian and seasonal systems: from photoneuroendocrinology to circadian biology and medicine.Cell and tissue research · 2025Review
- Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythms and sleep.PLoS biology · 2025Article
- USP8 and Hsp70 regulate endoreplication by synergistically promoting Fzr deubiquitination and stabilization.Science advances · 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
- Alternative splicing ofbioRxiv : the preprint server for biology · 2024Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- Ataxin2 functions via CrebA to mediate Huntingtin toxicity in circadian clock neurons.PLoS genetics · 2019Article
- GIGANTEA recruits the UBP12 and UBP13 deubiquitylases to regulate accumulation of the ZTL photoreceptor complex.Nature communications · 2019Article
- Article
- AMP-Activated Protein Kinase Regulates Circadian Rhythm by Affecting CLOCK inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
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- Modulation of miR-210 alters phasing of circadian locomotor activity and impairs projections of PDF clock neurons in Drosophila melanogaster.PLoS genetics · 2018Article
- Cardinal Epigenetic Role of non-coding Regulatory RNAs in Circadian Rhythm.Molecular neurobiology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A conserved transcriptional feedback loop underlies animal circadian rhythms. In Drosophila, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate the transcription of direct target genes like period (per) and timeless (tim). They encode the proteins PER and TIM, respectively, which repress CLK/CYC activity. Previous work indicates that repression is due to a direct PER-CLK/CYC interaction as well as CLK/CYC phosphorylation. We describe here the role of ubiquitin-specific protease 8 (USP8) in circadian transcriptional repression as well as the importance of CLK ubiquitylation in CLK/CYC transcription activity. usp8 loss of function (RNAi) or expression of a dominant-negative form of the protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly locomotor activity rhythms. Clock protein and mRNA molecular oscillations are virtually absent within circadian neurons of USP8-DN flies. Furthermore, CLK ubiquitylation cycles robustly in wild-type flies and peaks coincident with maximal CLK/CYC transcription. As USP8 interacts with CLK and expression of USP8-DN increases CLK ubiquitylation, the data indicate that USP8 deubiquitylates CLK, which down-regulates CLK/CYC transcriptional activity. Taken together with the facts that usp8 mRNA cycles and that its transcription is activated directly by CLK/CYC, USP8, like PER and TIM, contributes to the transcriptional feedback loop cycle that underlies circadian rhythms.
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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.