Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Department of Chemistry, University of Southern California, Los Angeles, CA 90089, USA.
Open Biol. 2024 Oct;14(10):240209. doi: 10.1098/rsob.240209. Epub 2024 Oct 30.
Cells must rapidly adapt to changes in nutrient conditions through responsive signalling cascades to maintain homeostasis. One of these adaptive pathways results in the post-translational modification of proteins by O-GlcNAc. O-GlcNAc modifies thousands of nuclear and cytoplasmic proteins in response to nutrient availability through the hexosamine biosynthetic pathway. O-GlcNAc is highly dynamic and can be added and removed from proteins multiple times throughout their life cycle, setting it up to be an ideal regulator of cellular processes in response to metabolic changes. Here, we describe the link between cellular metabolism and O-GlcNAc, and we explore O-GlcNAc's role in regulating cellular processes in response to nutrient levels. Specifically, we discuss the mechanisms of elevated O-GlcNAc levels in contributing to diabetes and cancer, as well as the role of decreased O-GlcNAc levels in neurodegeneration. These studies form a foundational understanding of aberrant O-GlcNAc in human disease and provide an opportunity to further improve disease identification and treatment.
细胞必须通过响应信号级联迅速适应营养条件的变化，以维持体内平衡。这些适应性途径之一导致蛋白质通过 O-GlcNAc 的翻译后修饰。O-GlcNAc 通过己糖胺生物合成途径响应营养可用性修饰数千种核和细胞质蛋白。O-GlcNAc 非常动态，可以在蛋白质的整个生命周期中多次添加和去除，使其成为响应代谢变化的细胞过程的理想调节剂。在这里，我们描述了细胞代谢与 O-GlcNAc 之间的联系，并探讨了 O-GlcNAc 在响应营养水平调节细胞过程中的作用。具体来说，我们讨论了升高的 O-GlcNAc 水平在糖尿病和癌症中的作用机制，以及 O-GlcNAc 水平降低在神经退行性变中的作用。这些研究为人类疾病中异常的 O-GlcNAc 提供了基础理解，并为进一步改善疾病识别和治疗提供了机会。
