J Cell Sci. 2010 Jan 1;123(Pt 1):13-22. doi: 10.1242/jcs.053678.
A paradigm-changing discovery in biology came about when it was found that nuclear and cytosolic proteins could be dynamically glycosylated with a single O-linked beta-N-acetylglucosamine (O-GlcNAc) moiety. O-GlcNAcylation is akin to phosphorylation: it occurs on serine and/or threonine side chains of proteins, and cycles rapidly upon cellular activation. O-GlcNAc and phosphate show a complex interplay: they can either competitively occupy a single site or proximal sites, or noncompetitively occupy different sites on a substrate. Phosphorylation regulates O-GlcNAc-cycling enzymes and, conversely, O-GlcNAcylation controls phosphate-cycling enzymes. Such crosstalk is evident in all compartments of the cell, a finding that is congruent with the fundamental role of O-GlcNAc in regulating nutrient- and stress-induced signal transduction. O-GlcNAc transferase is recruited to the plasma membrane in response to insulin and is targeted to substrates by forming transient holoenzyme complexes that have different specificities. Cytosolic O-GlcNAcylation is important for the proper transduction of signaling cascades such as the NFkappaB pathway, whereas nuclear O-GlcNAc is crucial for regulating the activity of numerous transcription factors. This Commentary focuses on recent findings supporting an emerging concept that continuous crosstalk between phosphorylation and O-GlcNAcylation is essential for the control of vital cellular processes and for understanding the mechanisms that underlie certain neuropathologies.
当发现核蛋白和胞质蛋白可以用单一的 O-连接的 β-N-乙酰葡萄糖胺（O-GlcNAc）部分进行动态糖基化时，生物学领域发生了一场范式转变的发现。O-GlcNAcylation 类似于磷酸化：它发生在蛋白质的丝氨酸和/或苏氨酸侧链上，并在细胞激活时快速循环。O-GlcNAc 和磷酸显示出复杂的相互作用：它们可以竞争占据单个位点或邻近位点，或者非竞争地占据底物上的不同位点。磷酸化调节 O-GlcNAc 循环酶，反之亦然，O-GlcNAcylation 控制磷酸循环酶。这种串扰在细胞的所有隔室中都很明显，这一发现与 O-GlcNAc 在调节营养和应激诱导的信号转导中的基本作用是一致的。O-GlcNAc 转移酶在胰岛素的作用下被招募到质膜上，并通过形成具有不同特异性的瞬时全酶复合物来靶向底物。细胞质中的 O-GlcNAcylation 对于 NFkappaB 途径等信号转导途径的正确转导很重要，而核中的 O-GlcNAc 对于调节许多转录因子的活性至关重要。本评论重点介绍了最近的发现，这些发现支持了一个新兴概念，即磷酸化和 O-GlcNAcylation 之间的持续串扰对于控制重要的细胞过程以及理解某些神经病理学机制至关重要。
