ArticleNucleic acids research2014
The E3 ubiquitin ligase UBE3A is an integral component of the molecular circadian clock through regulating the BMAL1 transcription factor.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Phosphorylation and Circadian Molecular Timing.Frontiers in physiology · 2020Pooled it
- Epigenetic Insights and Exosome-Based Therapeutics for Insomnia: Bridging Sleep Biology and Precision Medicine.Molecular neurobiology · 2026Review
- Circadian regulation of extracellular vesicle biogenesis, composition, and release.Npj biological timing and sleep · 2025Review
- Molecular aspects of Angelman Syndrome: Defining the new path forward.Biomolecules & biomedicine · 2025Review
- A preclinical pig model of Angelman syndrome mirrors the early developmental trajectory of the human condition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- Rbbp6-Mediated Bmal1 Ubiquitination Inhibits YAP1 Signaling Pathway to Promote Ferroptosis in Diabetes-Induced Testicular Damage.Diabetes & metabolism journal · 2025Article
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- E3 ubiquitin ligase UBR5 modulates circadian rhythm by facilitating the ubiquitination and degradation of the key clock transcription factor BMAL1.Acta pharmacologica Sinica · 2024Article
- UBE3A: The Role in Autism Spectrum Disorders (ASDs) and a Potential Candidate for Biomarker Studies and Designing Therapeutic Strategies.Diseases (Basel, Switzerland) · 2023Review
- Ferroptosis, autophagy, tumor and immunity.Heliyon · 2023Review
- Article
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- Article
- Circadian Rhythms and Sleep Are Dependent Upon Expression Levels of Key Ubiquitin LigaseFrontiers in behavioral neuroscience · 2022Article
- Exploring the Genomic Patterns in Human and Mouse Cerebellums Via Single-Cell Sequencing and Machine Learning Method.Frontiers in genetics · 2022Article
- Circadian Synchrony: Sleep, Nutrition, and Physical Activity.Frontiers in network physiology · 2021Article
- Methamphetamine-induced changes in myocardial gene transcription are sex-dependent.BMC genomics · 2021Article
- Cellular degradation systems in ferroptosis.Cell death and differentiation · 2021Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Post-translational modifications (such as ubiquitination) of clock proteins are critical in maintaining the precision and robustness of the evolutionarily conserved circadian clock. Ubiquitination of the core clock transcription factor BMAL1 (brain and muscle Arnt-like 1) has recently been reported. However, it remains unknown whether BMAL1 ubiquitination affects circadian pacemaking and what ubiquitin ligase(s) is involved. Here, we show that activating UBE3A (by expressing viral oncogenes E6/E7) disrupts circadian oscillations in mouse embryonic fibroblasts, measured using PER2::Luc dynamics, and rhythms in endogenous messenger ribonucleic acid and protein levels of BMAL1. Over-expression of E6/E7 reduced the level of BMAL1, increasing its ubiquitination and proteasomal degradation. UBE3A could bind to and degrade BMAL1 in a ubiquitin ligase-dependent manner. This occurred both in the presence and absence of E6/E7. We provide in vitro (knockdown/over-expression in mammalian cells) and in vivo (genetic manipulation in Drosophila) evidence for an endogenous role of UBE3A in regulating circadian dynamics and rhythmic locomotor behaviour. Together, our data reveal an essential and conserved role of UBE3A in the regulation of the circadian system in mammals and flies and identify a novel mechanistic link between oncogene E6/E7-mediated cell transformation and circadian (BMAL1) disruption.
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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.