Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses
Name
Vander Heiden_Inhibition of.pdf
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Author(s)
Vander Heiden, Matthew G.
Anastasiou, Dimitrios
Poulogiannis, George
Asara, John M.
Boxer, Matthew B.
Jiang, Jian-kang
Shen, Min
Gary, Bellinger
Sasaki, Atsuo T.
Locasale, Jason W.
Date Issued
November 2011
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Anastasiou, D., G. Poulogiannis, J. M. Asara, M. B. Boxer, J.-k. Jiang, M. Shen, G. Bellinger, et al. “Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes to Cellular Antioxidant Responses.” Science 334, no. 6060 (December 1, 2011): 1278-1283.
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Author's final manuscript
Abstract
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 Cys[superscript 358]. 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 Cys[superscript 358] to Ser[superscript 358] 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1126/science.1211485
