PDF(Pubmed)
Abstract：
Cells continuously fine-tune signaling pathway proteins to match nutrient and stress levels in their local environment by modifying intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) sugars, an essential process for cell survival and growth. The small size of these monosaccharide modifications poses a challenge for functional determination, but the chemistry and biology communities have together created a collection of precision tools to study these dynamic sugars. This review presents the major themes by which O-GlcNAc influences signaling pathway proteins, including G-protein coupled receptors, growth factor signaling, mitogen-activated protein kinase (MAPK) pathways, lipid sensing, and cytokine signaling pathways. Along the way, we describe in detail key chemical biology tools that have been developed and applied to determine specific O-GlcNAc roles in these pathways. These tools include metabolic labeling, O-GlcNAc-enhancing RNA aptamers, fluorescent biosensors, proximity labeling tools, nanobody targeting tools, O-GlcNAc cycling inhibitors, light-activated systems, chemoenzymatic labeling, and nutrient reporter assays. An emergent feature of this signaling pathway meta-analysis is the intricate interplay between O-GlcNAc modifications across different signaling systems, underscoring the importance of O-GlcNAc in regulating cellular processes. We highlight the significance of O-GlcNAc in signaling and the role of chemical and biochemical tools in unraveling distinct glycobiological regulatory mechanisms. Collectively, our field has determined effective strategies to probe O-GlcNAc roles in biology. At the same time, this survey of what we do not yet know presents a clear roadmap for the field to use these powerful chemical tools to explore cross-pathway O-GlcNAc interactions in signaling and other major biological pathways.
摘要：
细胞通过用O-连接的N-乙酰葡糖胺（O-GlcNAc）糖修饰细胞内蛋白，不断微调信号通路蛋白以匹配其局部环境中的营养和应激水平，细胞存活和生长的基本过程。这些单糖修饰的小尺寸对功能测定提出了挑战，但是化学和生物界共同创造了一系列精密工具来研究这些动态糖。这篇综述介绍了O-GlcNAc影响信号通路蛋白的主要主题，包括G蛋白偶联受体，生长因子信号，MAPK途径，脂质传感，和细胞因子信号通路。一路上,我们详细描述了已经开发并应用于确定这些途径中特定O-GlcNAc作用的关键化学生物学工具。这些工具包括代谢标签，O-GlcNAc增强RNA适体，荧光生物传感器，接近标签工具，纳米抗体靶向工具，O-GlcNAc循环抑制剂，光激活系统，化学酶标记，和营养报告检测。该信号通路荟萃分析的一个新兴特征是O-GlcNAc修饰在不同信号传导系统之间的复杂相互作用，强调O-GlcNAc在调节细胞过程中的重要性。我们强调了O-GlcNAc在信号传导中的重要性以及化学和生化工具在揭示不同糖生物学调节机制中的作用。总的来说，我们的领域已经确定了有效的策略来探索O-GlcNAc在生物学中的作用。同时,这项我们还不知道的调查为该领域提供了一个清晰的路线图，可以使用这些强大的化学工具来探索信号传导和其他主要生物学途径中的交叉途径O-GlcNAc相互作用。
