Chemical Immunology Lab, Centre for Cooperative Research in Biosciences, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Biscay, Spain.
Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
Front Immunol. 2023 Jan 26;13:1089824. doi: 10.3389/fimmu.2022.1089824. eCollection 2022.
The -linked β--acetylglucosamine (-GlcNAc) glycosylation of proteins is an essential and dynamic post-translational modification in mammalian cells that is regulated by the action of two enzymes. -GlcNAc transferase (OGT) incorporates this monosaccharide on serine/threonine residues, whereas -GlcNAcase (OGA) removes it. This modification is found on thousands of intracellular proteins involved in vital cellular processes, both under physiological and pathological conditions. Aberrant expression of -GlcNAc has been implicated in diseases such as Alzheimer, diabetes, and cancer, and growing evidence over the last decade has also revealed key implications of -GlcNAcylation in immunity. While some key signaling pathways involving -GlcNAcylation in immune cells have been discovered, a complete mechanistic understanding of how -GlcNAcylated proteins function in the immune system remains elusive, partly because of the difficulties in mapping and quantifying -GlcNAc sites. In this minireview, we discuss recent progress on chemical biology tools and approaches to investigate the role of -GlcNAcylation in immune cells, with the intention of encouraging further research and developments in chemical glycoimmunology that can advance our understanding of -GlcNAc in immunity.
蛋白质的 - 链接 β--乙酰氨基葡萄糖(-GlcNAc)糖基化是哺乳动物细胞中一种重要且动态的翻译后修饰,受两种酶的作用调节。-GlcNAc 转移酶(OGT)将这种单糖结合到丝氨酸/苏氨酸残基上,而 -GlcNAcase(OGA)则将其去除。这种修饰存在于数千种参与重要细胞过程的细胞内蛋白质上,无论是在生理还是病理条件下。-GlcNAc 的异常表达与阿尔茨海默病、糖尿病和癌症等疾病有关,过去十年的大量证据也揭示了 -GlcNAcylation 在免疫中的关键作用。虽然已经发现了免疫细胞中涉及 -GlcNAcylation 的一些关键信号通路,但 -GlcNAcylated 蛋白质在免疫系统中的功能的完整机制理解仍然难以捉摸,部分原因是在映射和量化 -GlcNAc 位点方面存在困难。在这篇综述中,我们讨论了化学生物学工具和方法在研究 -GlcNAcylation 在免疫细胞中的作用方面的最新进展,旨在鼓励在化学糖免疫学方面进一步研究和发展,从而增进我们对免疫中 -GlcNAc 的理解。