Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and Odontology, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Cells. 2021 Apr 27;10(5):1026. doi: 10.3390/cells10051026.
The reversible posttranslational -GlcNAc modification of serine or threonine residues of intracellular proteins is involved in many cellular events from signaling cascades to epigenetic and transcriptional regulation. -GlcNAcylation is a conserved nutrient-dependent process involving two enzymes, with -GlcNAc transferase (OGT) adding -GlcNAc and with -GlcNAcase (OGA) removing it in a manner that's protein- and context-dependent. -GlcNAcylation is essential for epigenetic regulation of gene expression through its action on Polycomb and Trithorax and COMPASS complexes. However, the important role of -GlcNAc in adult life and health span has been largely unexplored, mainly due the lack of available model systems. Cataloging the -GlcNAc proteome has proven useful in understanding the biology of this modification in vivo. In this study, we leveraged a recently developed knockout fly mutant to identify the -GlcNAcylated proteins in adult . The adult -GlcNAc proteome revealed many proteins related to cell and organismal growth, development, differentiation, and epigenetics. We identified many -GlcNAcylated proteins that play a role in increased growth and decreased longevity, including HCF, SIN3A, LOLA, KISMET, ATX2, SHOT, and FOXO. Interestingly, mutant flies are larger and have a shorter life span compared to wild type flies, suggesting increased -GlcNAc results in increased growth. Our results suggest that -GlcNAc alters the function of many proteins related to transcription, epigenetic modification and signaling pathways that regulate growth rate and longevity. Therefore, our findings highlight the importance of -GlcNAc in growth and life span in adult .
丝氨酸或苏氨酸残基的可逆翻译后 -GlcNAc 修饰参与了从信号级联到表观遗传和转录调控的许多细胞事件。-GlcNAc 化是一种保守的、依赖营养的过程，涉及两种酶，其中 -GlcNAc 转移酶（OGT）添加 -GlcNAc，而 -GlcNA 酶（OGA）以依赖于蛋白质和上下文的方式去除它。-GlcNAc 化对于通过其对 Polycomb 和 Trithorax 和 COMPASS 复合物的作用对基因表达的表观遗传调控至关重要。然而，由于缺乏可用的模型系统，-GlcNAc 在成年期和健康跨度中的重要作用在很大程度上仍未得到探索。 -GlcNAc 蛋白质组的编目已被证明有助于理解这种修饰在体内的生物学。在这项研究中，我们利用最近开发的 敲除果蝇突变体来鉴定成年果蝇中的 -GlcNAc 化蛋白。成年 -GlcNAc 蛋白质组揭示了许多与细胞和生物体生长、发育、分化和表观遗传学相关的蛋白质。我们鉴定了许多参与生长增加和寿命缩短的 -GlcNAc 化蛋白，包括 HCF、SIN3A、LOLA、KISMET、ATX2、SHOT 和 FOXO。有趣的是，与野生型果蝇相比， 突变体果蝇更大，寿命更短，这表明 -GlcNAc 增加导致生长增加。我们的结果表明，-GlcNAc 改变了许多与转录、表观遗传修饰和信号通路相关的蛋白质的功能，这些蛋白质调节生长速度和寿命。因此，我们的发现强调了 -GlcNAc 在成年期生长和寿命中的重要性。
