Vosseller K, Wells L, Hart G W
Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
Biochimie. 2001 Jul;83(7):575-81. doi: 10.1016/s0300-9084(01)01295-0.
The molecular complexity that defines different cell types and their biological responses occurs at the level of the cell's proteome. The recent increase in availability of genomic sequence information is a valuable tool for the field of proteomics. While most proteomic studies focus on differential expression levels, post-translational modifications such as phosphorylation, glycosylation, and acetylation, provide additional levels of functional complexity to the cell's proteome. The reversible post-translational modification O-linked beta-N-acetylglucosamine (O-GlcNAc) is found on serines and threonines of nuclear and cytoplasmic proteins. It appears to be as widespread as phosphorylation. While phosphorylation is recognized as a fundamental mechanism for controlling protein function, less is known about the specific roles of O-GlcNAc modification. However, evidence is building that O-GlcNAc may compete with phosphate at some sites of attachment. Aberrant O-GlcNAc modification has been linked to several disease states, including diabetes and Alzheimer's disease. Regulated enzymes catalyzing the addition (O-GlcNAc transferase, OGT) and removal (O-GlcNAcase) of the modification have been cloned and OGT is required for life at the single cell level. Here we review the properties of O-GlcNAc that suggest it is a regulatory modification analogous to phosphorylation. We also discuss the use of comparative functional proteomics to elucidate functions for this ubiquitous intracellular carbohydrate modification.
定义不同细胞类型及其生物学反应的分子复杂性发生在细胞蛋白质组水平。基因组序列信息可用性的近期增加是蛋白质组学领域的一个有价值工具。虽然大多数蛋白质组学研究集中在差异表达水平上，但诸如磷酸化、糖基化和乙酰化等翻译后修饰为细胞蛋白质组提供了额外的功能复杂性层次。可逆的翻译后修饰O-连接的β-N-乙酰葡糖胺（O-GlcNAc）存在于核蛋白和细胞质蛋白的丝氨酸和苏氨酸上。它似乎与磷酸化一样广泛存在。虽然磷酸化被认为是控制蛋白质功能的基本机制，但关于O-GlcNAc修饰的具体作用知之甚少。然而，越来越多的证据表明，O-GlcNAc可能在某些附着位点与磷酸竞争。异常的O-GlcNAc修饰与几种疾病状态有关，包括糖尿病和阿尔茨海默病。催化该修饰添加（O-GlcNAc转移酶，OGT）和去除（O-GlcNAcase）的调控酶已被克隆，并且OGT在单细胞水平上是生命所必需的。在这里，我们综述了O-GlcNAc的特性，这些特性表明它是一种类似于磷酸化的调控修饰。我们还讨论了使用比较功能蛋白质组学来阐明这种普遍存在的细胞内碳水化合物修饰的功能。
