Journal
MOLECULAR CELL
Volume 42, Issue 6, Pages 719-730Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.04.025
Keywords
-
Categories
Funding
- NCET [09-0315]
- NSFC [30600112, 30871255, 31071192]
- 985 Program
- Shanghai key project [09JC1402300]
- 100 Talents Programme of Shanghai Health
- Shanghai Leading Academic Discipline Project [B110]
- National Institutes of Health (NIH)
- [2009CB918401]
- [2011CB910600]
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available