title: The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids.
abstract: 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.g. determination of protein stability and half-life) and cellular level (e.g. influenza infection). Sia are synthesized in the cytosol from UDP-GlcNAc by the Roseman-Warren pathway. The key enzyme of this pathway is the UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sia are transferred on glycoconjugates by a family of Golgi-located enzymes, so called sialyltransferases (ST). There are 20 (human) ST known, which all transfer CMP-activated Sia to specific acceptor-sites on glycoconjugates. The regulation of the expression of ST is still not understood. Using a GNE-deficient embryonic stem cell line, which cannot synthesize Sia endogenously and by supplementation of soluble Sia precursors, we present data that the cellular availability of Sia strongly regulates the expression of ST on the level of transcription. In summary, we suggest that the concentration of the donor substrate of sialyltransferases, which can be regarded as a sensor for the environmental conditions of a cell, regulates not only total sialylation, but also the quality of sialylation. This allows a cell to response to altered environmental conditions.
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bork
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Wenke
authors.initials: W
authors.lastname: Weidemann
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Berneck
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kuchta
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Dorit
authors.initials: D
authors.lastname: Bennmann
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Thate
authors.affiliation: Institute for Biochemistry II, Nonnenplan 2-4, D-07743 Jena, Germany.
authors.forename: Otmar
authors.initials: O
authors.lastname: Huber
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany.
authors.forename: Vinayaga S
authors.initials: VS
authors.lastname: Gnanapragassam
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystraße 1, D-06114 Halle (Saale), Germany. Electronic address: ruediger.horstkorte@medizin.uni-halle.de.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
mesh_terms: D000818:Animals; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000096:biosynthesis*; D011499:Protein Processing, Post-Translational; D012799:Sialyltransferases / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012799:Sialyltransferases; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; D019158:N-Acetylneuraminic Acid
keywords: Glycosylation; Mouse embryonic stem cells; Sialic acid; Sialyltransferases