ArticleThe Journal of biological chemistry2013
Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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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
32 citing papers in PubMed, 59 citations in OpenAlex.
- Urinary ANGPTL3: a novel noninvasive biomarker for podocyte injury in pediatric glomerular diseases.Journal of translational medicine · 2026Article
- Angiopoietin-like 3 monomers are abundant in human plasma but are unable to inhibit endothelial lipase.JCI insight · 2025Article
- The Biology and Clinical Implications of PCSK7.Endocrine reviews · 2025Review
- ANGPTL3 and residual atherosclerotic risk: from lipid metabolism to therapeutic targeting.Frontiers in endocrinology · 2025Review
- Functional Roles of Furin in Cardio-Cerebrovascular Diseases.ACS pharmacology & translational science · 2024Review
- ANGPTL3 negatively regulates IL-1β-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.Journal of molecular cell biology · 2024Article
- Angiopoietin-like 3: An important protein in regulating lipoprotein levels.Best practice & research. Clinical endocrinology & metabolism · 2023Review
- Angiopoietin-like proteins inhibitors: New horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia.Cardiology journal · 2023Article
- ANGPTL3 as a Drug Target in Hyperlipidemia and Atherosclerosis.Current atherosclerosis reports · 2022Review
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- COVID-19 liver and gastroenterology findings: AnWorld journal of hepatology · 2022Article
- An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif.Journal of lipid research · 2022Article
- Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8.American journal of physiology. Endocrinology and metabolism · 2021Review
- The Lipid-Modulating Effect of Tangeretin on the Inhibition of Angiopoietin-like 3 (ANGPTL3) Gene Expression through Regulation of LXRα Activation in Hepatic Cells.International journal of molecular sciences · 2021Article
- Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia.International journal of molecular sciences · 2021Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity.Frontiers in cell and developmental biology · 2021Review
- GALNT2 regulates ANGPTL3 cleavage in cells and in vivo of mice.Scientific reports · 2020Article
- Angiopoietin-Like 3: From Discovery to Therapeutic Gene Editing.JACC. Basic to translational science · 2019Review
- Angiopoietin-like 4 promotes the intracellular cleavage of lipoprotein lipase by PCSK3/furin in adipocytes.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions. Their knock-out (KO) in mice resulted in strong and specific phenotypes demonstrating that, in vivo, these PCs are unique and essential during development. However, they also exhibit redundant functions. Liver angiopoietin-like 3 (ANGPTL3) inhibits lipolysis by binding to lipoprotein lipases. It is found in the plasma as full length and truncated forms. The latter is more active and generated by cleavage at a furin-like site. Endothelial lipase (EL) binds heparin sulfate proteoglycans on cell surfaces and catalyzes the hydrolysis of HDL phospholipids. EL activity is regulated by two endogenous inhibitors, ANGPTL3 and ANGPTL4, and by PCs that inactivate EL through cleavage releasing the N-terminal catalytic and C-terminal lipid-binding domains. Herein, because furin and PC5/6 complete KOs are lethal, we used mice lacking furin or PC5/6 specifically in hepatocytes (hKO) or mice completely lacking PACE4. In primary hepatocytes, ANGPTL3 was processed into a shorter form of ANGPTL3 intracellularly by furin only, and extracellularly mainly by PACE4. In vivo, the absence of furin in hepatocytes reduced by ∼50% the circulating levels of cleaved ANGPTL3, while the lack of PACE4 had only a minor effect. Analysis of the EL processing in primary hepatocytes and in vivo revealed that it is mostly cleaved by furin. However, the lack of furin or PC5/6 in hepatocytes and complete PACE4 KO did not appreciably modify plasma HDL levels or EL activity. Thus, inhibition of furin in liver would not be expected to modify the plasma lipid profiles.
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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.