Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth

By Lei Lv, Dong Li, Di Zhao, Ruiting Lin, Yajing Chu, Heng Zhang, Zhengyu Zha, Ying Liu, Z. Li, Yan-ping Xu and 5 more. Molecules and Cells, 2011

609 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Cancer Research, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/032b28d00f9148d92b453ead689eb3bc196e6f6e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Patrick S. Ward
2. Craig B. Thompson
3. Ivana Samaržija
4. Ralph J. Deberardinis
5. M. V. Vander Heiden
6. Navdeep S. Chandel
7. Jason W. Locasale
8. Alec C. Kimmelman

In Epidemiology

1. Craig B. Thompson
2. Beth Levine
3. Guido Kroemer

In Molecular Biology

1. Patrick S. Ward
2. Craig B. Thompson
3. Ivana Samaržija
4. Ralph J. Deberardinis
5. M. V. Vander Heiden
6. David M. Sabatini
7. Navdeep S. Chandel
8. Jason W. Locasale

Citations in the corpus

• Post-Translational Modifications That Drive Prostate Cancer Progression (2021, background): “KAT2B Promotes PKM2 acetylation and decreases PKM2 protein level through degradation through chaperone-mediated autophagy; promotes tumor growth [309]”
• Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “Another report showed that PKM2 has a unique lysine residue which is acetylated in tumor cells, targeting it for degradation by chaperone-mediated autophagy (Lv et al., 2011).”