Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
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Stefan O. Reinke
Abstract
The key enzyme for the biosynthesis of N-acetylneuraminic acid, from which all other sialic acids are formed, is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). GNE is a highly conserved protein found throughout the animal kingdom. Its highest expression is seen in the liver and placenta. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. GNE knock-out in mice leads to embryonic lethality, emphasizing the crucial role of this key enzyme for sialic acid biosynthesis. The metabolic capacity to synthesize sialic acid and CMP-sialic acid upon ManNAc loads is amazingly high. An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. Due to the importance of increased concentrations of tumor-surface sialic acid, first attempts to find inhibitors of GNE have been successful.
©2009 by Walter de Gruyter Berlin New York
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- Guest Editorial
- Highlight: Perspectives in glycobiology
- Cell biology and glycosylation: protein targeting by O- and N-linked glycosylation
- Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases
- Glycosylation pattern of brush border-associated glycoproteins in enterocyte-like cells: involvement of complex-type N-glycans in apical trafficking
- Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase
- MUC1 traverses apical recycling endosomes along the biosynthetic pathway in polarized MDCK cells
- Cell biology and glycosylation: carbohydrate-mediated recognition and signaling in cell proliferation and differentiation
- From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans
- Brain development needs sugar: the role of polysialic acid in controlling NCAM functions
- Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells
- Glycosylation and disease
- Management of the human mucosal defensive barrier: evidence for glycan legislation
- Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
- GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells
- Tumor-associated MUC1 glycopeptide epitopes are not subject to self-tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice
- Protein-specific glycosylation and its control
- Protein-specific glycosylation: signal patches and cis-controlling peptidic elements
- O-glycosylation pattern of CD24 from mouse brain
- Advancements in analytical techniques
- Carbohydrate microarrays: key developments in glycobiology
- On-line nano-HPLC/ESI QTOF MS monitoring of α2–3 and α2–6 sialylation in granulocyte glycosphingolipidome
Artikel in diesem Heft
- Guest Editorial
- Highlight: Perspectives in glycobiology
- Cell biology and glycosylation: protein targeting by O- and N-linked glycosylation
- Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases
- Glycosylation pattern of brush border-associated glycoproteins in enterocyte-like cells: involvement of complex-type N-glycans in apical trafficking
- Impact of glycosylation and detergent-resistant membranes on the function of intestinal sucrase-isomaltase
- MUC1 traverses apical recycling endosomes along the biosynthetic pathway in polarized MDCK cells
- Cell biology and glycosylation: carbohydrate-mediated recognition and signaling in cell proliferation and differentiation
- From structural to functional glycomics: core substitutions as molecular switches for shape and lectin affinity of N-glycans
- Brain development needs sugar: the role of polysialic acid in controlling NCAM functions
- Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells
- Glycosylation and disease
- Management of the human mucosal defensive barrier: evidence for glycan legislation
- Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis
- GD3 synthase overexpression enhances proliferation and migration of MDA-MB-231 breast cancer cells
- Tumor-associated MUC1 glycopeptide epitopes are not subject to self-tolerance and improve responses to MUC1 peptide epitopes in MUC1 transgenic mice
- Protein-specific glycosylation and its control
- Protein-specific glycosylation: signal patches and cis-controlling peptidic elements
- O-glycosylation pattern of CD24 from mouse brain
- Advancements in analytical techniques
- Carbohydrate microarrays: key developments in glycobiology
- On-line nano-HPLC/ESI QTOF MS monitoring of α2–3 and α2–6 sialylation in granulocyte glycosphingolipidome
