Very Ninon, Vercoutter-Edouart Anne-Sophie, Lefebvre Tony, Hardivillé Stéphan, El Yazidi-Belkoura Ikram
Université Lille, CNRS, UMR 8576-UGSF-Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
Front Endocrinol (Lausanne). 2018 Oct 9;9:602. doi: 10.3389/fendo.2018.00602. eCollection 2018.
The hexosamine biosynthetic pathway (HBP) and the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway are considered as nutrient sensors that regulate several essential biological processes. The hexosamine biosynthetic pathway produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the substrate for -GlcNAc transferase (OGT), the enzyme that -GlcNAcylates proteins on serine (Ser) and threonine (Thr) residues. -linked β-N-acetylglucosaminylation (-GlcNAcylation) and phosphorylation are highly dynamic post-translational modifications occurring at the same or adjacent sites that regulate folding, stability, subcellular localization, partner interaction, or activity of target proteins. Here we review recent evidence of a cross-regulation of PI3K/AKT/mTOR signaling pathway and protein -GlcNAcylation. Furthermore, we discuss their co-dysregulation in pathological conditions, e.g., cancer, type-2 diabetes (T2D), and cardiovascular, and neurodegenerative diseases.
己糖胺生物合成途径（HBP）和磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路被认为是调节多种重要生物学过程的营养传感器。己糖胺生物合成途径产生尿苷二磷酸N-乙酰葡糖胺（UDP-GlcNAc），它是O-连接N-乙酰葡糖胺转移酶（OGT）的底物，该酶可将蛋白质的丝氨酸（Ser）和苏氨酸（Thr）残基进行O-连接N-乙酰葡糖胺化修饰。O-连接β-N-乙酰葡糖胺化修饰（O-GlcNAcylation）和磷酸化是发生在相同或相邻位点的高度动态的翻译后修饰，可调节靶蛋白的折叠、稳定性、亚细胞定位、相互作用伙伴或活性。在此，我们综述了PI3K/AKT/mTOR信号通路与蛋白质O-GlcNAcylation交叉调节的最新证据。此外，我们还讨论了它们在癌症、2型糖尿病（T2D）以及心血管和神经退行性疾病等病理状态下的共同失调情况。
