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Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Antioxidant Responses

shuzhang 添加于 2011-12-15 09:52 | 1486 次阅读 | 0 个评论

作者
Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang J-k., Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, Thomas CJ, Vander Heiden MG, Cantley LC
摘要
Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys358. This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys358 to Ser358 oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress.
详细资料
- 文献种类:期刊
- 期刊名称: Science
- 期刊缩写: Science
- ISBN: 0036-8075
标签

ROS
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