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

Lessons from GNE-deficient embryonic stem cells: sialic acid biosynthesis is involved in proliferation and gene expression
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DOI:
10.1093/glycob/cwp153
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发表时间:
2010-01-01
期刊:
影响因子:
4.3
通讯作者:
Horstkorte, Ruediger
Horstkorte, Ruediger
中科院分区:
生物学3区
文献类型:
--
作者:
Weidemann, Wenke;Klukas, Christian;Horstkorte, Ruediger

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唾液酸是真核细胞糖缀合物的末端糖基。它们参与多种细胞功能,如细胞粘附或信号识别。唾液酸生物合成的关键酶是双功能的UDP-N-乙酰葡糖胺-2-差向异构酶/N-乙酰甘露糖胺激酶(GNE),其催化唾液酸在胞质溶胶中生物合成的前两个步骤。GNE失活导致早期胚胎死亡。在这项研究中,我们分析了野生型和GNE缺陷的小鼠胚胎干细胞。我们首次发现增殖与GNE表达和细胞唾液酸浓度直接相关。此外,我们确定了生长相关的基因,在GNE缺陷的胚胎干细胞与野生型胚胎干细胞相比,差异表达。
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. Inactivation of GNE causes early embryonic lethality. In this study, we analyzed wild-type and GNE-deficient embryonic stem cells from mice. We found for the first time that proliferation is directly correlated with GNE-expression and the cellular sialic acid concentration. Furthermore, we identified growth-related genes that are differentially expressed in GNE-deficient embryonic stem cells compared to wildtype embryonic stem cells.