O-GlcNAcylation: a bridge between glucose and cell differentiation.
O-GlcNAcylation: a bridge between glucose and cell differentiation.
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O-GlcNAcylation：葡萄糖和细胞分化之间的桥梁。
DOI：
10.1111/jcmm.12807
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发表时间：
2016-05
影响因子：
5.3
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Sun C;Shang J;Yao Y;Yin X;Liu M;Liu H;Zhou Y
葡萄糖是大多数细胞的主要能量供应和关键代谢物，在细胞分化时尤其重要。高浓度或低浓度的葡萄糖通过胰岛素、转化生长因子-β和过氧化物酶体增殖物激活受体γ途径等增强或抑制细胞的成骨、软骨和脂肪分化。新的证据表明己糖胺生物合成途径是葡萄糖通量、细胞信号传导和细胞分化的表观遗传调控之间串扰的介质。细胞外葡萄糖通量通过己糖胺生物合成途径改变细胞内 O-GlcNAc 酰化水平。对细胞分化重要的信号分子，包括蛋白激酶 C、细胞外信号调节激酶、Runx2、CCAAT/增强子结合蛋白，均通过 O-GlcNAcylation 进行修饰。因此，O-GlcNAc 酰化通过蛋白质的转录后修饰显着改变分化过程中的细胞命运。此外，O-GlcNAc 酰化和磷酸化在细胞分化过程中表现出复杂的相互作用：它们可以非竞争性地占据基质上的不同位点，也可以竞争性地占据单个位点或邻近位点。因此，葡萄糖通过 O-GlcNAc 酰化对细胞分化的影响为控制衰老和疾病中的组织稳态和再生提供了潜在的靶标。在这里，我们回顾了建立葡萄糖浓度、O-GlcNAcNAc水平和细胞分化之间新兴关系的最新进展。
Glucose is the major energy supply and a critical metabolite for most cells and is especially important when cell is differentiating. High or low concentrations of glucose enhances or inhibits the osteogenic, chondrogenic and adipogenic differentiation of cell via the insulin, transforming growth factor‐β and peroxisome proliferator‐activated receptor γ pathways, among others. New evidence implicates the hexosamine biosynthetic pathway as a mediator of crosstalk between glucose flux, cellular signalling and epigenetic regulation of cell differentiation. Extracellular glucose flux alters intracellular O‐GlcNAcylation levels through the hexosamine biosynthetic pathway. Signalling molecules that are important for cell differentiation, including protein kinase C, extracellular signal‐regulated kinase, Runx2, CCAAT/enhancer‐binding proteins, are modified by O‐GlcNAcylation. Thus, O‐GlcNAcylation markedly alters cell fate during differentiation via the post‐transcriptional modification of proteins. Furthermore, O‐GlcNAcylation and phosphorylation show complex interactions during cell differentiation: they can either non‐competitively occupy different sites on a substrate or competitively occupy a single site or proximal sites. Therefore, the influence of glucose on cell differentiation via O‐GlcNAcylation offers a potential target for controlling tissue homoeostasis and regeneration in ageing and disease. Here, we review recent progress establishing an emerging relationship among glucose concentration, O‐GlcNAcylation levels and cell differentiation.