ArticleThe Journal of biological chemistry2011
Improvement of dolichol-linked oligosaccharide biosynthesis by the squalene synthase inhibitor zaragozic acid.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Repurposing the HMG-CoA reductase inhibitor atorvastatin for SRD5A3-congenital disorder of glycosylation.Communications medicine · 2026Article
- Quantification of Dolichyl Phosphates Using Phosphate Methylation and Reverse-Phase Liquid Chromatography-High Resolution Mass Spectrometry.Analytical chemistry · 2023Article
- Inhibition of Orbivirus Replication by Fluvastatin and Identification of the Key Elements of the Mevalonate Pathway Involved.Viruses · 2021Article
- Lysosomal cholesterol accumulation contributes to the movement phenotypes associated with NUS1 haploinsufficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- The Lec5 glycosylation mutant links homeobox genes with cholesterol and lipid-linked oligosaccharides.Glycobiology · 2019Article
- The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis.Journal of cell science · 2019Article
- Article
- cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases.The Journal of biological chemistry · 2016Review
- Squalestatin is an inhibitor of carotenoid biosynthesis in Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2015Article
- A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines.Immunity, inflammation and disease · 2014Article
- Article
- Regulation of dolichol-linked glycosylation.Glycoconjugate journal · 2013Review
- A zebrafish model of PMM2-CDG reveals altered neurogenesis and a substrate-accumulation mechanism for N-linked glycosylation deficiency.Molecular biology of the cell · 2012Article
- Life with too much polyprenol: polyprenol reductase deficiency.Molecular genetics and metabolism · 2012Article
- Insights into complexity of congenital disorders of glycosylation.Biochemia medica · 2012Review
- Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of congenital disorders of glycosylation (CDG) are caused by defects of dolichol (Dol)-linked oligosaccharide assembly, which lead to under-occupancy of N-glycosylation sites. Most mutations encountered in CDG are hypomorphic, thus leaving residual activity to the affected biosynthetic enzymes. We hypothesized that increased cellular levels of Dol-linked substrates might compensate for the low biosynthetic activity and thereby improve the output of protein N-glycosylation in CDG. To this end, we investigated the potential of the squalene synthase inhibitor zaragozic acid A to redirect the flow of the polyisoprene pathway toward Dol by lowering cholesterol biosynthesis. The addition of zaragozic acid A to CDG fibroblasts with a Dol-P-Man synthase defect led to the formation of longer Dol-P species and to increased Dol-P-Man levels. This treatment was shown to decrease the pathologic accumulation of incomplete Dol pyrophosphate-GlcNAc(2)Man(5) in Dol-P-Man synthase-deficient fibroblasts. Zaragozic acid A treatment also decreased the amount of truncated protein N-linked oligosaccharides in these CDG fibroblasts. The increased cellular levels of Dol-P-Man and possibly the decreased cholesterol levels in zaragozic acid A-treated cells also led to increased availability of the glycosylphosphatidylinositol anchor as shown by the elevated cell-surface expression of the CD59 protein. This study shows that manipulation of the cellular Dol pool, as achieved by zaragozic acid A addition, may represent a valuable approach to improve N-linked glycosylation in CDG cells.
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