文章：

癌症中2-氧戊二酸依赖的双加氧酶

2-Oxoglutarate-dependent dioxygenases in cancer

原文发布日期：2020-10-21

DOI: 10.1038/s41568-020-00303-3

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

2-酮戊二酸依赖性双加氧酶（2OGDDs）是一个酶超家族，在多种生物过程中发挥重要作用，包括调节缺氧诱导因子介导的缺氧适应、细胞外基质形成、基因转录的表观遗传调控以及细胞代谢重编程。所有2OGDDs都需要氧气、还原态铁和2-酮戊二酸（又称α-酮戊二酸）才能发挥作用，但它们对这些共底物的亲和力及其对特定共底物耗竭的敏感度存在显著差异。许多2OGDDs在癌症中经常出现功能失调。此外，癌症特异性代谢变化（例如琥珀酸脱氢酶、延胡索酸水合酶或异柠檬酸脱氢酶编码基因突变后发生的变化）可导致特定2OGDDs功能紊乱。后一发现表明，2OGDDs在癌症中的作用不仅限于编码2OGDD超家族成员的基因存在突变的癌症。本文综述了正常细胞中2OGDDs的调控机制，以及该调控在癌症中如何被破坏。

原文链接：

2-Oxoglutarate-dependent dioxygenases in cancer