Tools for functional dissection of site-specific O-GlcNAcylation,RSC Chemical Biology

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Tools for functional dissection of site-specific O-GlcNAcylation
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2020-06-12 , DOI: 10.1039/d0cb00052c
Andrii Gorelik ₁ , Daan M F van Aalten _{1,

2}

Affiliation

Protein O-GlcNAcylation is an abundant post-translational modification of intracellular proteins with the monosaccharide N-acetylglucosamine covalently tethered to serines and threonines. Modification of proteins with O-GlcNAc is required for metazoan embryo development and maintains cellular homeostasis through effects on transcription, signalling and stress response. While disruption of O-GlcNAc homeostasis can have detrimental impact on cell physiology and cause various diseases, little is known about the functions of individual O-GlcNAc sites. Most of the sites are modified sub-stoichiometrically which is a major challenge to the dissection of O-GlcNAc function. Here, we discuss the application, advantages and limitations of the currently available tools and technologies utilised to dissect the function of O-GlcNAc on individual proteins and sites in vitro and in vivo. Additionally, we provide a perspective on future developments required to decipher the protein- and site-specific roles of this essential sugar modification.

中文翻译：

位点特异性 O-GlcNAc 化功能解析的工具

蛋白质 O-GlcNAc 酰化是细胞内蛋白质的一种丰富的翻译后修饰，单糖N-乙酰氨基葡萄糖与丝氨酸和苏氨酸共价连接。用 O-GlcNAc 修饰蛋白质是后生动物胚胎发育所必需的，并通过影响转录、信号传导和应激反应来维持细胞稳态。虽然 O-GlcNAc 稳态的破坏会对细胞生理学产生不利影响并导致各种疾病，但人们对各个 O-GlcNAc 位点的功能知之甚少。大多数位点都经过亚化学计量修饰，这对 O-GlcNAc 功能的剖析是一个重大挑战。在这里，我们讨论了当前可用的工具和技术的应用、优点和局限性，这些工具和技术用于在体外和体内剖析 O-GlcNAc 对单个蛋白质和位点的功能。此外，我们还对破译这种重要糖修饰的蛋白质和位点特异性作用所需的未来发展提供了展望。

更新日期：2020-08-06

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