Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Current address: GSK, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
Chembiochem. 2020 Jun 2;21(11):1647-1655. doi: 10.1002/cbic.201900719. Epub 2020 Mar 3.
The hypoxia-inducible factors (HIFs) are key transcription factors in determining cellular responses involving alterations in protein levels in response to limited oxygen availability in animal cells. 2-Oxoglutarate-dependent oxygenases play key roles in regulating levels of HIF and its transcriptional activity. We describe MS-based proteomics studies in which we compared the results of subjecting human breast cancer MCF-7 cells to hypoxia or treating them with a cell-penetrating derivative (dimethyl N-oxalylglycine; DMOG) of the stable 2OG analogue N-oxalylglycine. The proteomic results are consistent with reported transcriptomic analyses and support the proposed key roles of 2OG-dependent HIF prolyl- and asparaginyl-hydroxylases in the hypoxic response. Differences between the data sets for hypoxia and DMOG might reflect context-dependent effects or HIF-independent effects of DMOG.
缺氧诱导因子 (HIFs) 是决定细胞反应的关键转录因子，涉及动物细胞中因氧气供应有限而导致的蛋白质水平变化。2-氧戊二酸依赖性加氧酶在调节 HIF 及其转录活性水平方面发挥着关键作用。我们描述了基于 MS 的蛋白质组学研究，在这些研究中，我们比较了将人乳腺癌 MCF-7 细胞置于缺氧环境或用稳定的 2OG 类似物 N-草酰甘氨酸的细胞穿透衍生物（二甲基 N-草酰基甘氨酸；DMOG）处理后的结果。蛋白质组学结果与已报道的转录组学分析一致，并支持 2OG 依赖性 HIF 脯氨酰和天冬酰胺羟化酶在缺氧反应中的关键作用。缺氧和 DMOG 数据集之间的差异可能反映了依赖于背景的效应或 DMOG 对 HIF 不依赖的效应。
