ArticleMolecular and cellular biology2014
The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol synthesis pathway.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024Pooled it
- Protein M of NADC30-like PRRSV induces MARCH6-mediated K33-linked polyubiquitination of SLA-DRA.The Journal of biological chemistry · 2026Article
- Review
- Low temperature rather than hypoxia drives cholesterol synthesis and oxygen consumption in plateau zokors.iScience · 2026Article
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Loss of the E3 ubiquitin ligase MARCHF6 alters hepatic lipid metabolism and drives spontaneous hepatosteatosis.Molecular metabolism · 2026Article
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Article
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- MARCH6 suppresses Tembusu virus replication by targeting viral NS5 protein for TOLLIP-mediated selective autophagic degradation.Journal of virology · 2025Article
- The Ac/N-Degron Domain of MARCHF6 E3 Ubiquitin Ligase and Its Role in Regulating Ferroptosis.Cells · 2025Review
- Membrane-associated ring-CH-type finger 2 protects against metabolic dysfunction-associated fatty liver disease by targeting fatty acid synthase.Molecular metabolism · 2025Article
- Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endoplasmic reticulum-associated degradation mitigates atherosclerosis by maintaining cellular homeostasis.Frontiers in physiology · 2025Review
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- Glutamine sensing licenses cholesterol synthesis.The EMBO journal · 2024Article
- Squalene monooxygenase (SQLE) protects ovarian cancer cells from ferroptosis.Scientific reports · 2024Article
- A suite of genome-engineered hepatic cells provides novel insights into the spatiotemporal metabolism of apolipoprotein B and apolipoprotein B-containing lipoprotein secretion.Cardiovascular research · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mevalonate pathway is used by cells to produce sterol and nonsterol metabolites and is subject to tight metabolic regulation. We recently reported that squalene monooxygenase (SM), an enzyme controlling a rate-limiting step in cholesterol biosynthesis, is subject to cholesterol-dependent proteasomal degradation. However, the E3-ubiquitin (E3) ligase mediating this effect was not established. Using a candidate approach, we identify the E3 ligase membrane-associated RING finger 6 (MARCH6, also known as TEB4) as the ligase controlling degradation of SM. We find that MARCH6 and SM physically interact, and consistent with MARCH6 acting as an E3 ligase, its overexpression reduces SM abundance in a RING-dependent manner. Reciprocally, knockdown of MARCH6 increases the level of SM protein and prevents its cholesterol-regulated degradation. Additionally, this increases cell-associated SM activity but is unexpectedly accompanied by increased flux upstream of SM. Prompted by this observation, we found that knockdown of MARCH6 also controls the level of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) in hepatocytes and model cell lines. In conclusion, MARCH6 controls abundance of both SM and HMGCR, establishing it as a major regulator of flux through the cholesterol synthesis pathway.
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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.