ArticleThe Journal of biological chemistry2016
High Affinity Heme Binding to a Heme Regulatory Motif on the Nuclear Receptor Rev-erbβ Leads to Its Degradation and Indirectly Regulates Its Interaction with Nuclear Receptor Corepressor.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.Journal of cellular physiology · 2026Review
- Negative regulation of TbioRxiv : the preprint server for biology · 2026Article
- Article
- Unraveling the Interplay of Dopamine, Carbon Monoxide, and Heme Oxygenase in Neuromodulation and Cognition.ACS chemical neuroscience · 2024Review
- Article
- Timed use of digoxin prevents heart ischemia-reperfusion injury through a REV-ERBα-UPS signaling pathway.Nature cardiovascular research · 2022Article
- REV-ERB Agonist SR9009 Regulates the Proliferation and Neurite Outgrowth/Suppression of Cultured Rat Adult Hippocampal Neural Stem/Progenitor Cells in a Concentration-Dependent Manner.Cellular and molecular neurobiology · 2022Article
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Molecular regulations of circadian rhythm and implications for physiology and diseases.Signal transduction and targeted therapy · 2022Review
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Review
- Callyspongiolide kills cells by inducing mitochondrial dysfunction via cellular iron depletion.Communications biology · 2021Article
- HO-1 and Heme: G-Quadruplex Interaction Choreograph DNA Damage Responses and Cancer Growth.Cells · 2021Review
- Unravelling the mechanisms controlling heme supply and demand.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ.Science advances · 2021Article
- Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.The Journal of biological chemistry · 2020Article
- Scavenging of Labile Heme by Hemopexin Is a Key Checkpoint in Cancer Growth and Metastases.Cell reports · 2020Article
- The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation.The Journal of biological chemistry · 2020Article
- Interplay of Heme with Macrophages in Homeostasis and Inflammation.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Rev-erbα and Rev-erbβ are heme-binding nuclear receptors (NR) that repress the transcription of genes involved in regulating metabolism, inflammation, and the circadian clock. Previous gene expression and co-immunoprecipitation studies led to a model in which heme binding to Rev-erbα recruits nuclear receptor corepressor 1 (NCoR1) into an active repressor complex. However, in contradiction, biochemical and crystallographic studies have shown that heme decreases the affinity of the ligand-binding domain of Rev-erb NRs for NCoR1 peptides. One explanation for this discrepancy is that the ligand-binding domain and NCoR1 peptides used for in vitro studies cannot replicate the key features of the full-length proteins used in cellular studies. However, the combined in vitro and cellular results described here demonstrate that heme does not directly promote interactions between full-length Rev-erbβ (FLRev-erbβ) and an NCoR1 construct encompassing all three NR interaction domains. NCoR1 tightly binds both apo- and heme-replete FLRev-erbβ·DNA complexes; furthermore, heme, at high concentrations, destabilizes the FLRev-erbβ·NCoR1 complex. The interaction between FLRev-erbβ and NCoR1 as well as Rev-erbβ repression at the Bmal1 promoter appear to be modulated by another cellular factor(s), at least one of which is related to the ubiquitin-proteasome pathway. Our studies suggest that heme is involved in regulating the degradation of Rev-erbβ in a manner consistent with its role in circadian rhythm maintenance. Finally, the very slow rate constant (10(-6) s(-1)) of heme dissociation from Rev-erbβ rules out a prior proposal that Rev-erbβ acts as an intracellular heme sensor.
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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.