Inhibitors of N-glycosylation as a potential tool for analysis of the mechanism of action and cellular localisation of glycoprotein P.

Wójtowicz, Karolina; Szaflarski, Witold; Januchowski, Radosław; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

doi:10.18388/abp.2012_2076

Cited by 21 publications

(26 citation statements)

References 52 publications

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“…The protein with the sugar core attached is translocated to the Golgi apparatus, where terminal glycosylation occurs. The mature protein is then directed to its final destination [6,12].…”

mentioning

confidence: 99%

Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

Wójtowicz

Januchowski

Nowicki

et al. 2015

Biomedicine & Pharmacotherapy

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“…The protein with the sugar core attached is translocated to the Golgi apparatus, where terminal glycosylation occurs. The mature protein is then directed to its final destination [6,12].…”

mentioning

confidence: 99%

Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

Wójtowicz

Januchowski

Nowicki

et al. 2015

Biomedicine & Pharmacotherapy

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“…Moreover, specific sialylated N-glycoproteins were exclusively identified in biological fluids from EOC patients [42]. Aberrant N-glycosylation has been also involved in EOC chemoresistance, as N-glycosylation inhibitors were shown to markedly reduce multidrug resistance [43]. …”

Section: Discussionmentioning

confidence: 99%

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

Sheta

Woo

Roux‐Dalvai³

et al. 2016

Journal of Proteomics

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Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among women in the Western world than all other gynecologic malignancies. There is urgent need for new therapeutic targets and a better understanding of EOC initiation and progression. We have previously identified the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the GalNAc-transferases (GalNAc-Ts) gene family, as hypomethylated and overexpressed in high-grade serous EOC tumors, compared to low malignant potential EOC tumors and normal ovarian tissues. This data also suggested for a role of GALNT3 in aberrant EOC glycosylation, possibly implicated in disease progression. To evaluate differential glycosylation in EOC caused by modulations in GALNT3 expression, we used a metabolic labeling strategy for enrichment and mass spectrometry-based characterization of glycoproteins following GALNT3 gene knockdown (KD) in A2780s EOC cells. A total of 589 differentially expressed glycoproteins were identified upon GALNT3 KD. Most identified proteins were involved in mechanisms of cellular metabolic functions, post-translational modifications, and some have been reported to be implicated in EOC etiology. The GALNT3-dependent glycoproteins identified by this metabolic labeling approach support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as novel EOC biomarkers and/or therapeutic targets. Biological significance: Knowledge of the O-glycoproteome has been relatively elusive, and the functions of the individual polypeptide GalNAc-Ts have been poorly characterized. Alterations in GalNAc-Ts expression were shown to provide huge variability in the O-glycoproteome in various pathologies, including cancer. The application of a chemical biology approach for the metabolic labeling and subsequent characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has provided a strategy allowing for proteomic discovery of GalNAc-Ts specific functions. Our study supports an essential role of one of the GalNAc-Ts — GALNT3, in EOC dissemination, including its implication in modulating PTMs and EOC metabolism. Our approach validates the use of the applied metabolic strategy to identify important functions of GalNAc-Ts in normal and pathological conditions.

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“…Inhibition of N-glycosylation is a useful approach to study Nglycoprotein structure, distribution and function (17). Also, it is an important tool for examining the potential functional role(s) of Nglycans on specific proteins or intact cells.…”

Section: B-1 Inhibition Of N-glycosylationmentioning

confidence: 99%

“…3). Overall, these antibiotics have been widely used in a number of functional studies of N-glycosylation (6,13,17).…”

Section: B-1-1 Inhibition Of Dolichol-pp-glcnac Assemblymentioning

confidence: 99%

Chemical Regulation of Glycosylation Processes

Sun

2018

TIGG

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Glycans (monosaccharides and oligosaccharides) and their conjugates (glycoproteins, glycolipids, and proteoglycans) are structurally diverse biomolecules that are involved in many biological processes of health and disease. The structural diversity of glycans and glycoconjugates is owed to their monosaccharide composition, anomeric state, glycosidic linkage, modification (phosphorylation, sulfation, acetylation, etc.) and aglycone (protein, lipid, etc.). These diverse structures are controlled by complex glycosylation processes in cells, which are mediated by various glycosyltransferases and glycosidases. Glycosylation processes can be chemically regulated by inhibition of glycosyltransferases or glycosidases with natural and synthetic molecules. Treatment of cells with inhibitors of these enzymes results in the production of glycans or glycoconjugates containing missing or altered glycan chains. This approach is highly useful for examining the potential functional role(s) of glycans and glycoconjugates in cells or tissues, and in biological processes of health and disease. Eventually, it will provide novel mechanisms for disease treatment. This review highlights recent developments in chemical regulation of glycosylation processes with specific targets including: inhibition of (1) Nglycosylation, (2) O-glycosylation, (3) O-linked GlcNAc glycosylation, (4) proteoglycan biosynthesis, (5) glycolipid biosynthesis, and (6) terminal glycosylation. The goal of this review is to provide researchers with more competent choices in their research and lay a foundation on which continued advancements can be made to promote further explorations in glycoscience and biomedical research and applications.

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Inhibitors of N-glycosylation as a potential tool for analysis of the mechanism of action and cellular localisation of glycoprotein P.

Cited by 21 publications

References 52 publications

Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

A metabolic labeling approach for glycoproteomic analysis reveals altered glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells

Chemical Regulation of Glycosylation Processes

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