异柠檬酸脱氢酶 2 (IDH2) 在癌症中的表观遗传失调。

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Anuraj Nayarisseri, Srinivas Bandaru, Arshiya Khan, Khushboo Sharma, Anushka Bhrdwaj, Manmeet Kaur, Dipannita Ghosh, Ishita Chopra, Aravind Panicker, Abhishek Kumar, Priyadevi Saravanan, Pranoti Belapurkar, Francisco Jaime Bezerra Mendonça Junior, Sanjeev Kumar Singh
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引用次数: 0

摘要

全基因组研究的最新进展揭示了许多由参与细胞代谢的基因引起的表观遗传调控。异柠檬酸脱氢酶(IDH)是一种主要在三羧酸(TCA)循环中将异柠檬酸转化为-酮戊二酸(KG)的重要酶,由于其在细胞代谢途径中的重要作用而变得尤为重要。IDH1、IDH2 和 IDH3 是三种异构的 IDH 酶,已被证明能调节细胞代谢。特别重要的是,IDH2 基因与多种癌症有关,包括胶质瘤、少突胶质瘤和星形细胞瘤。这些基因突变会导致产生副代谢产物 D-2-羟基戊二酸(D-2-HG),它在细胞中积累会促进肿瘤生长。D-2-HG水平的提高会竞争性地抑制α-KG依赖酶,抑制细胞TCA循环,上调与细胞生长和存活相关的HIF-1α通路,促进DNA高甲基化相关的表观遗传活性,所有这些协同作用都会导致癌变。本综述讨论了细胞中 IDH2 调控的表观遗传学机制及其进一步的临床意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).

Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.

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来源期刊
Advances in protein chemistry and structural biology
Advances in protein chemistry and structural biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
7.40
自引率
0.00%
发文量
66
审稿时长
>12 weeks
期刊介绍: Published continuously since 1944, The Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics.
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