ArticleProceedings of the National Academy of Sciences of the United States of America2015
Ubiquitin ligase Siah2 regulates RevErbα degradation and the mammalian circadian clock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Circadian rhythms and lung cancer biology and immunotherapy: Emerging opportunities and challenges.Chinese medical journal pulmonary and critical care medicine · 2026Review
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- SIAH2 suppresses c-JUN pathway by promoting the polyubiquitination and degradation of HBx in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2024Article
- Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.International journal of molecular sciences · 2024Article
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- Timed use of digoxin prevents heart ischemia-reperfusion injury through a REV-ERBα-UPS signaling pathway.Nature cardiovascular research · 2022Article
- Timed use of cardiac glycoside protects the heart.Nature cardiovascular research · 2022Article
- Death of a Protein: The Role of E3 Ubiquitin Ligases in Circadian Rhythms of Mice and Flies.International journal of molecular sciences · 2022Review
- "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".PLoS genetics · 2022Article
- Reciprocal regulation of chaperone-mediated autophagy and the circadian clock.Nature cell biology · 2021Article
- Chaperone-mediated autophagy on the clock.Nature cell biology · 2021Article
- The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA.Current research in neurobiology · 2021Article
- Micro RNAs and the biological clock: a target for diseases associated with a loss of circadian regulation.African health sciences · 2020Article
- The Lineage Before Time: Circadian and Nonclassical Clock Influences on Development.Annual review of cell and developmental biology · 2020Review
- Systems Level Understanding of Circadian Integration with Cell Physiology.Journal of molecular biology · 2020Review
- Molecular mechanisms and physiological importance of circadian rhythms.Nature reviews. Molecular cell biology · 2020Review
- The E3 Ligases Spsb1 and Spsb4 Regulate RevErbα Degradation and Circadian Period.Journal of biological rhythms · 2019Article
- Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice.Cellular and molecular life sciences : CMLS · 2018Article
- Systems Chronotherapeutics.Pharmacological reviews · 2017Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Regulated degradation of proteins by the proteasome is often critical to their function in dynamic cellular pathways. The molecular clock underlying mammalian circadian rhythms relies on the rhythmic expression and degradation of its core components. However, because the tools available for identifying the mechanisms underlying the degradation of a specific protein are limited, the mechanisms regulating clock protein degradation are only beginning to be elucidated. Here we describe a cell-based functional screening approach designed to quickly identify the ubiquitin E3 ligases that induce the degradation of potentially any protein of interest. We screened the nuclear hormone receptor RevErbα (Nr1d1), a key constituent of the mammalian circadian clock, for E3 ligases that regulate its stability and found Seven in absentia2 (Siah2) to be a key regulator of RevErbα stability. Previously implicated in hypoxia signaling, Siah2 overexpression destabilizes RevErbα/β, and siRNA depletion of Siah2 stabilizes endogenous RevErbα. Moreover, Siah2 depletion delays circadian degradation of RevErbα and lengthens period length. These results demonstrate the utility of functional screening approaches for identifying regulators of protein stability and reveal Siah2 as a previously unidentified circadian clockwork regulator that mediates circadian RevErbα turnover.
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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.