The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth
Open accessAbstract
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.
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Cites
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“Both lysosome binding and uptake assays were carried out as described previously (Cuervo et al., 2004).”
Methodp53 Regulates Mitochondrial Respiration
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Pyruvate kinase M2 is a phosphotyrosine-binding protein
Christofk, H. R., Vander Heiden, M. G., Wu, N., Asara, J. M., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06667 · Cited by 995
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Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth
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Chaperone-mediated autophagy: selectivity pays off
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“Both HSC70 and LAMP2A are critical components in the CMA pathway (Cuervo, 2009).”
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Cited by
Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate
Ward, P. S., & Thompson, C. B. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.014 · Cited by 3,233
Autophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Lactate metabolism in human health and disease
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01151-3 · Cited by 1,454
The coming of age of chaperone-mediated autophagy
Kaushik, S., & Cuervo, A. M. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0001-6 · Cited by 1,407
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335
Metadata
- Authors
- Lv, L., Li, D., Zhao, D., Lin, R., Chu, Y., Zhang, H., Zha, Z., Liu, Y., Li, Z., Xu, Y., Wang, G., Huang, Y., Xiong, Y., Guan, K.-L., & Lei, Q.-Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 42
- Issue
- 6
- Pages
- 719-730
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2089551665
- Cited by
- 610
- References
- 10
- FWCI
- 13.05
- Type
- journal article
- Language
- en
- Open access
- bronze
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