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首页> 外文期刊>Nature immunology >Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy
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Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy

机译：葡萄糖和谷氨酰胺燃料蛋白O-Glcnacylation控制T细胞自我更新和恶性肿瘤

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摘要

Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We found that glutamine and glucose also fuel an indispensable dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for cellular glycosyltransferases. Immune-activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-linked-beta-N-acetylglucosamine (O-GlcNAc) glycosyltransferase as compared with naive cells. We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation via regulation of glucose and glutamine transport. Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation and peripheral T cell clonal expansion. Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology.
机译：持续葡萄糖和谷氨酰胺转运对于活化的T淋巴细胞是必不可少的，以支持ATP和大分子生物合成。我们发现谷氨酰胺和葡萄糖还促进T细胞发育，转化和分化的关键阶段的细胞内蛋白质O-GlcNylation的不可或缺的动态调节。葡萄糖和谷氨酰胺是尿苷二磷酸N-乙酰葡糖胺（UDP-GLCNAc）的前体，用于细胞糖基转移酶的基材。与幼稚细胞相比，免疫活化的T细胞含有较高浓度的UDP-GlcNAc和由酶O型β-乙酰戊酰胺（O-GlcNAc）糖基转移酶控制的细胞内蛋白质O-甘氨酸溶液。通过调节葡萄糖和谷氨酰胺运输，我们鉴定了Notch，T细胞抗原受体和C-Myc作为T细胞蛋白O-甘烷化的关键控制器。 O-GlcNAc转移酶的丧失阻断T细胞祖细胞更新，恶性转化和外周T细胞克隆膨胀。因此，由O-GlcNAC糖基转移酶调节的营养依赖性信号传导途径是T细胞生物学的基础。

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