The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids
The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids
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DOI：
10.1016/j.gep.2017.03.003
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发表时间：
2017-01-01
影响因子：
1.2
通讯作者：
Horstkorte, Ruediger
中科院分区：
文献类型：
--
作者：
Bork, Kaya;Weidemann, Wenke;Horstkorte, Ruediger
糖基化是蛋白质翻译后最常见和最重要的修饰。它发生在特定的共有序列上，但特定聚糖的最终结构不是在DNA上编码的，而是取决于所需酶的表达和底物（活化单糖）的可用性。唾液酸（Sia）是大多数糖蛋白或糖脂（=糖缀合物）的末端单糖，并且在分子水平（例如确定蛋白质稳定性和半衰期）和细胞水平（例如流感感染）上参与多种功能。Sia在胞质溶胶中通过Roseman-Warren途径由UDP-GlcNAc合成。该途径的关键酶是UDP-GlcNAc 2-差向异构酶/ManNAc激酶（GNE）。Sia通过位于高尔基体的酶家族（所谓的唾液酸转移酶（ST））转移到糖缀合物上。已知有20种（人）ST，它们都将CMP活化的Sia转移到糖缀合物上的特异性受体位点。ST基因表达的调控机制尚不清楚。使用GNE缺陷的胚胎干细胞系，它不能合成Sia内源性和补充可溶性Sia前体，我们目前的数据表明，Sia的细胞利用率强烈调节ST的表达在转录水平上。总之，我们认为，唾液酸转移酶的供体底物的浓度，这可以被视为一个传感器的环境条件的细胞，调节不仅总唾液酸化，而且唾液酸化的质量。这使得细胞能够对改变的环境条件做出反应。(C)2017爱思唯尔B. V.保留所有权利。
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. (C) 2017 Elsevier B.V. All rights reserved.