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      Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.

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          Abstract

          Most tumor cells take up more glucose than normal cells but metabolize glucose via glycolysis even in the presence of normal levels of oxygen, a phenomenon known as the Warburg effect. Tumor cells commonly express the embryonic M2 isoform of pyruvate kinase (PKM2) that may contribute to the metabolism shift from oxidative phosphorylation to aerobic glycolysis and tumorigenesis. Here we show that PKM2 is acetylated on lysine 305 and that this acetylation is stimulated by high glucose concentration. PKM2 K305 acetylation decreases PKM2 enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy (CMA). Acetylation increases PKM2 interaction with HSC70, a chaperone for CMA, and association with lysosomes. Ectopic expression of an acetylation mimetic K305Q mutant accumulates glycolytic intermediates and promotes cell proliferation and tumor growth. These results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and CMA.

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          Author and article information

          Journal
          Mol Cell
          Molecular cell
          Elsevier BV
          1097-4164
          1097-2765
          Jun 24 2011
          : 42
          : 6
          Affiliations
          [1 ] Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University, Shanghai 200032, China.
          Article
          S1097-2765(11)00371-6 NIHMS784975
          10.1016/j.molcel.2011.04.025
          4879880
          21700219
          2cb42153-82a5-4d77-a9c2-1e7c2f02829c
          Copyright © 2011 Elsevier Inc. All rights reserved.

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