表观遗传学
延胡索酶
基因
转录因子
异柠檬酸脱氢酶
重编程
生物
细胞生物学
遗传学
酶
生物化学
作者
Julie-Aurore Losman,Peppi Koivunen,William G. Kaelin
出处
期刊:Nature Reviews Cancer
[Springer Nature]
日期:2020-10-21
卷期号:20 (12): 710-726
被引量:129
标识
DOI:10.1038/s41568-020-00303-3
摘要
2-Oxoglutarate-dependent dioxygenases (2OGDDs) are a superfamily of enzymes that play diverse roles in many biological processes, including regulation of hypoxia-inducible factor-mediated adaptation to hypoxia, extracellular matrix formation, epigenetic regulation of gene transcription and the reprogramming of cellular metabolism. 2OGDDs all require oxygen, reduced iron and 2-oxoglutarate (also known as α-ketoglutarate) to function, although their affinities for each of these co-substrates, and hence their sensitivity to depletion of specific co-substrates, varies widely. Numerous 2OGDDs are recurrently dysregulated in cancer. Moreover, cancer-specific metabolic changes, such as those that occur subsequent to mutations in the genes encoding succinate dehydrogenase, fumarate hydratase or isocitrate dehydrogenase, can dysregulate specific 2OGDDs. This latter observation suggests that the role of 2OGDDs in cancer extends beyond cancers that harbour mutations in the genes encoding members of the 2OGDD superfamily. Herein, we review the regulation of 2OGDDs in normal cells and how that regulation is corrupted in cancer. This Review discusses the metabolic regulation of 2-oxoglutarate-dependent dioxygenases (2OGDDs) and how dysregulation of 2OGDDs in cancer, by genetic aberrations or environmental factors including hypoxia and/or the action of oncometabolites, can contribute to tumour development and growth.
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