The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids.

Glycosylation is the most frequent and important post-translational modification of proteins. It occurs on specific consensus sequences but the final structure of a particular glycan is not coded on the DNA, rather it depends on the expression of the required enzymes and the availability of substrates (activated monosaccharides). Sialic acid (Sia) is the terminal monosaccharide of most glycoproteins or glycolipids (= glycoconjugates) and involved in a variety of function on molecular (e.

Aberrant O-GlcNAcylation disrupts GNE enzyme activity in GNE myopathy.

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme for the biosynthesis of sialic acids. Sialic acids are terminal monosaccharides of glycoconjugates and gangliosides, which have an essential influence on various cell interactions. The sialylation of proteins varies during development, aging, and pathogenesis of degenerative diseases such as Morbus Alzheimer, diabetes mellitus type II, or myopathies.

Sialylation and muscle performance: sialic acid is a marker of muscle ageing.

Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates. They are involved in many cellular functions, such as cell-cell interaction and signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol.

The key enzyme of the sialic acid metabolism is involved in embryoid body formation and expression of marker genes of germ layer formation.

The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice.

UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis.

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is the key enzyme of sialic acid biosynthesis in vertebrates. It catalyzes the first two steps of the cytosolic formation of CMP-N-acetylneuraminic acid from UDP-N-acetylglucosamine. In this review we give an overview of structure, biochemistry, and genetics of the bifunctional enzyme and its complex regulation.

Biochemical characterization of the M712T-mutation of the UDP-N-acetylglucosamine 2-epimerase/N-acetyl-mannosaminekinase in hereditary inclusion body myopathy.

Hereditary inclusion body myopathy is a neuromuscular disorder characterized by muscle weakness with a late onset and slow progression. It is caused by mutations of the gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE). One of the most frequent mutations is an exchange of methionine to threonine at position 712 (M712T).

Lessons from GNE-deficient embryonic stem cells: sialic acid biosynthesis is involved in proliferation and gene expression.

Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. They are involved in a variety of cellular functions, such as cell adhesion or signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol.

Beyond glycosylation: sialic acid precursors act as signaling molecules and are involved in cellular control of differentiation of PC12 cells.

Sialic acids represent a family of 9-carbon acidic amino sugars expressed mainly as terminal monosaccharides on most mammalian glycoconjugates. Sialic acids play an outstanding role during cellular processes, such as development and regeneration, as they are involved in a variety of molecular interactions. Sialic acids are synthesized in the cytosol starting from UDP-N-acetylglucosamine by the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE), which is the key enzyme in the biosynthesis of sialic acid that catalyzes the generation of N-acetylmannosamine, which in turn is an intermediate of the sialic acid pathway that represents the natural molecular precursor of all sialic acids.

Increasing the sialylation of therapeutic glycoproteins: the potential of the sialic acid biosynthetic pathway.

The number of therapeutic proteins has increased dramatically over the past years and most of the therapeutic proteins in the market today are glycoproteins. Usually, recombinant glycoproteins are produced in mammalian cell lines, such as Chinese-hamster-ovary-cells to obtain mammalian-type of glycosylation. The terminal monosaccharide of N-linked complex glycans is typically occupied by sialic acid.

The key enzyme of sialic acid biosynthesis (GNE) promotes neurite outgrowth of PC12 cells.

Axonal outgrowth is a prerequisite for the development of the most complex organ, the brain. It depends partially on the attachment of sialic acid on glycans of (sialo)-glycoproteins expressed on the plasma membrane. In our study, we showed that nerve growth factor-induced neurite outgrowth of PC12-cells enhances the expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase (GNE), the key enzyme for the biosynthesis of sialic acid.

Experimental approaches to interfere with the polysialylation of the neural cell adhesion molecule in vitro and in vivo.

Sialic acid (Sia) is expressed as terminal sugar in many glycoconjugates and plays an important role during development and regeneration. Addition of homopolymers of Sia (polysialic acid; polySia/PSA) is a unique and highly regulated post-translational modification of the neural cell adhesion molecule (NCAM). The presence of polySia affects NCAM-dependent cell adhesion and plays an important role during brain development, neural regeneration, and plastic processes including learning and memory.

N-propanoylmannosamine interferes with O-GlcNAc modification of the tyrosine 3-monooxygenase and stimulates dopamine secretion.

The most consistent neurochemical abnormality in Parkinson's disease is degeneration of dopaminergic neurons in the substantia nigra, leading to a reduction of striatal dopamine levels. The rate-limiting step in the biosynthesis of dopamine, noradrenalin, and adrenalin is catalyzed by tyrosine 3-monooxygenase (=tyrosine hydroxylase), which catalyzes the formation of L-DOPA. In earlier studies, we demonstrated that the novel synthetic sialic acid precursor N-propanoylmannosamine is a potent stimulator of axonal growth and promotes reestablishment of the perforant pathway from layer II of cortical neurons to the outer molecular layer of the dentate gyrus.

Enhanced sialylation of EPO by overexpression of UDP-GlcNAc 2-epimerase/ManAc kinase containing a sialuria mutation in CHO cells.

Sialylation (e.g. expression of sialic acid) plays a crucial role for function and stability of most glycoproteins.

Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice.

Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of eukaryotic cells. They are involved in a variety of cellular functions, such as cell adhesion or signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyzes the first two steps of sialic acid biosynthesis in the cytosol.

The collapsin response mediator protein 1 (CRMP-1) and the promyelocytic leukemia zinc finger protein (PLZF) bind to UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis.

Sialic acids (Sia) are expressed as terminal sugars in many glycoconjugates. They are involved in a variety of cell-cell interactions and therefore play an important role during development and regeneration. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme in the de novo synthesis of Sia and it is a regulator of cell surface sialylation.

Domain-specific characteristics of the bifunctional key enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase is a bifunctional enzyme, which initiates and regulates sialic acid biosynthesis. Sialic acids are important compounds of mammalian glycoconjugates, mediating several biological processes, such as cell-cell or cell-matrix interactions. In order to characterize the function of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, a number of deletion mutants were generated, lacking either parts of the N-terminal epimerase or the C-terminal kinase domain.