ArticleCell reports2022
A multienzyme S-nitrosylation cascade regulates cholesterol homeostasis.
Article in Cell reports, 2022. 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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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
19 citing papers in PubMed, 26 citations in OpenAlex.
- Remaking an exit: dynamic regulation of ER exit sites by post-translational modifications.Trends in cell biology · 2026Review
- Nitric oxide drives proteomic diversity through alternative splicing.Molecular cell · 2026Article
- Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.Redox biology · 2026Article
- Multi-omic analysis reveals nitric oxide dependent remodeling in classically activated macrophages and identifies negative regulation mediated by AKR1A1.bioRxiv : the preprint server for biology · 2026Article
- S-Nitrosylation of GPCR Regulatory Machinery as a Mechanism to Bias Signaling.Handbook of experimental pharmacology · 2026Review
- PCSK9 and Lipid Metabolism: Genetic Variants, Current Therapies, and Cardiovascular Outcomes.Cardiovascular drugs and therapy · 2025Review
- Article
- Dysregulated ProteinCirculation research · 2025Article
- S-nitrosylation of pVHL regulates βProceedings of the National Academy of Sciences of the United States of America · 2025Article
- S-Nitrosylation: Mechanistic Links between Nitric Oxide Signaling and Atherosclerosis.Current atherosclerosis reports · 2025Review
- The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming.bioRxiv : the preprint server for biology · 2025Article
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Gases define redox signalling: NO, HNature metabolism · 2025Article
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- Identification of Protein Targets ofACS chemical biology · 2024Article
- Article
- Comparison of the Nitric Oxide Synthase Interactomes and S-Nitroso-Proteomes: Furthering the Case for Enzymatic S-Nitrosylation.Antioxidants & redox signaling · 2023Article
- Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia.The Journal of clinical investigation · 2023Article
- Endothelial nitric oxide synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation.Frontiers in cardiovascular medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Accumulating evidence suggests that protein S-nitrosylation is enzymatically regulated and that specificity in S-nitrosylation derives from dedicated S-nitrosylases and denitrosylases that conjugate and remove S-nitrosothiols, respectively. Here, we report that mice deficient in the protein denitrosylase SCoR2 (S-nitroso-Coenzyme A Reductase 2; AKR1A1) exhibit marked reductions in serum cholesterol due to reduced secretion of the cholesterol-regulating protein PCSK9. SCoR2 associates with endoplasmic reticulum (ER) secretory machinery to control an S-nitrosylation cascade involving ER cargo-selection proteins SAR1 and SURF4, which moonlight as S-nitrosylases. SAR1 acts as a SURF4 nitrosylase and SURF4 as a PCSK9 nitrosylase to inhibit PCSK9 secretion, while SCoR2 counteracts nitrosylase activity by promoting PCSK9 denitrosylation. Inhibition of PCSK9 by an NO-based drug requires nitrosylase activity, and small-molecule inhibition of SCoR2 phenocopies the PCSK9-mediated reductions in cholesterol observed in SCoR2-deficient mice. Our results reveal enzymatic machinery controlling cholesterol levels through S-nitrosylation and suggest a distinct treatment paradigm for cardiovascular disease.
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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.