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

• DOI: 10.1126/science.1211485
• Publication Date: 2011-11-04T04:21:52Z
• Authors: Dimitrios Anastasiou; George Poulogiannis; John M. Asara; Matthew B. Boxer; Jian-kang Jiang; Min Shen; Gary Bellinger; Atsuo T. Sasaki; Jason W. Locasale; Douglas S. Auld; Craig J. Thomas; Matthew G. Vander...; Lewis C. Cantley
• Keywords: PKM2

Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cells, acute increases ROS caused inhibition the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation Cys(358). This PKM2 required to divert glucose flux into pentose phosphate pathway and thereby generate sufficient reducing potential detoxification ROS. Lung cells which endogenous was replaced with Cys(358) Ser(358) oxidation-resistant mutant exhibited increased sensitivity oxidative stress impaired tumor formation a xenograft model. Besides promoting metabolic changes proliferation, regulatory properties may confer an additional advantage by allowing them withstand stress.