Document Detail


Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth.
MedLine Citation:
PMID:  21700219     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Lei Lv; Dong Li; Di Zhao; Ruiting Lin; Yajing Chu; Heng Zhang; Zhengyu Zha; Ying Liu; Zi Li; Yanping Xu; Gang Wang; Yiran Huang; Yue Xiong; Kun-Liang Guan; Qun-Ying Lei
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular cell     Volume:  42     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  719-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology; Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; School of Life Science, Fudan University, Shanghai 200433, China.
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