ArticleThe Journal of biological chemistry2015
The Regulatory Domain of Squalene Monooxygenase Contains a Re-entrant Loop and Senses Cholesterol via a Conformational Change.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Low temperature rather than hypoxia drives cholesterol synthesis and oxygen consumption in plateau zokors.iScience · 2026Article
- Squalene Epoxidase: A Key Enzymatic Component in the Triterpenoid Biosynthesis Pathway.Applied biochemistry and biotechnology · 2026Review
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Peroxidation rate constants and mechanisms of isoprenoid-derived lipids and their roles in ferroptosis.Redox biochemistry and chemistry · 2025Article
- Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.Nature communications · 2024Article
- Review
- Exploring the "misfolding problem" by systematic discovery and analysis of functional-but-degraded proteins.Molecular biology of the cell · 2023Article
- Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene.Communications biology · 2023Article
- Hypoxia truncates and constitutively activates the key cholesterol synthesis enzyme squalene monooxygenase.eLife · 2023Article
- Lipid saturation induces degradation of squalene epoxidase for sterol homeostasis and cell survival.Life science alliance · 2023Article
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- Targeting the key cholesterol biosynthesis enzyme squalene monooxygenasefor cancer therapy.Frontiers in oncology · 2022Review
- How Is the Fidelity of Proteins Ensured in Terms of Both Quality and Quantity at the Endoplasmic Reticulum? Mechanistic Insights into E3 Ubiquitin Ligases.International journal of molecular sciences · 2021Review
- The Degron Architecture of Squalene Monooxygenase and How Specific Lipids Calibrate Levels of This Key Cholesterol Synthesis Enzyme.Advances in experimental medicine and biology · 2021Article
- Squalene and cholesterol in the balance at the ER membrane.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mechanisms and regulation of cholesterol homeostasis.Nature reviews. Molecular cell biology · 2020Review
- A key mammalian cholesterol synthesis enzyme, squalene monooxygenase, is allosterically stabilized by its substrate.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The cholesterol synthesis enzyme lanosterol 14α-demethylase is post-translationally regulated by the E3 ubiquitin ligase MARCH6.The Biochemical journal · 2020Article
- Non-canonical ubiquitination of the cholesterol-regulated degron of squalene monooxygenase.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Squalene monooxygenase (SM) is an important control point in cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase. Although it is known to associate with the endoplasmic reticulum, its topology has not been determined. We have elucidated the membrane topology of the sterol-responsive domain of SM comprising the first 100 amino acids fused to GFP (SM N100-GFP) by determining the accessibility of 16 introduced cysteines to the cysteine-reactive, membrane-impermeable reagent PEG-maleimide. We have identified a region integrally associated with the endoplasmic reticulum membrane that is likely to interact with cholesterol or respond to cholesterol-induced membrane effects. By comparing cysteine accessibility with and without cholesterol treatment, we further present evidence to suggest that cholesterol induces a conformational change in SM N100-GFP. This change is likely to lead to its targeted degradation by the ubiquitin-proteasome system because degradation is blunted by treatment with the chemical chaperone glycerol, which retains SM N100-GFP in its native conformation. Furthermore, degradation can be disrupted by insertion of two N-terminal myc tags, implicating the N terminus in this process. Together, this information provides new molecular insights into the regulation of this critical control point in cholesterol synthesis.
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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.