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蛋白质O-GlcNAc修饰与肿瘤糖代谢关系的研究进展

Advances of relationship between protein O-GlcNAcylation and glucose metabolism in tumors

  • 摘要: 蛋白质O-GlcNAc糖基化是指单个N-乙酰葡萄糖胺(N-acetylglucosamine,GlcNAc)分子连接在蛋白质丝氨酸或苏氨酸的羟基氧原子上的一种翻译后修饰。O-GlcNAc糖基化广泛存在于转录因子、代谢通路上的激酶以及细胞质的部分酶中,影响细胞的转录、信号的传导和细胞的代谢等生命进程。肿瘤的异常糖代谢是近年来肿瘤发病机制和治疗靶点研究领域的热点。O-GlcNAc糖基化通过影响代谢通路上激酶的活性进而调控肿瘤细胞的糖代谢,与肿瘤的糖代谢密切相关,被认为是肿瘤产生发展的潜在原因之一。本文就O-GlcNAc修饰在肿瘤葡萄糖摄取、糖酵解、戊糖磷酸途径及三羧酸循环等研究中的进展进行综述,为研发靶向O-GlcNAc修饰的抗肿瘤靶点及药物提供理论参考。

     

    Abstract: O-GlcNAcylation is the addition of a single N-acetylglucosamine(GlcNAc)moiety to the hydroxyl groups of serine or threonine residues of nuclear and cytoplasmic proteins. The transcription factors, kinases of the metabolic pathways and some cytoplasmic enzymes can be O-GlcNAcylated to affect cell transcription, signal transduction, cell metabolism and other biological functions. Abnormal glucose metabolism of tumors has been a hotspot in the research field of tumor pathogenesis and therapeutic targets recently. O-GlcNAclation regulates the glucose metabolism of tumor by affecting the activity of kinases in the metabolic pathway, which is closely associated with the abnormal glucose metabolism of tumor. The abnormal O-GlcNAcylation is one of the potential reasons of cancer. In this review, in order to provide a theoretical reference for developing anti-tumor targets and drugs targeting O-GlcNAc modification, we briefly summarized how O-GlcNAcylation regulated glucose metabolism on glucose metabolism, glucose uptake, glycolysis, pentose phosphate pathway and tricarboxylic acid cycle in cancer cell.

     

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