O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth Journal Article
| Authors: | Singh, J. P.; Qian, K.; Lee, J. S.; Zhou, J.; Han, X.; Zhang, B.; Ong, Q.; Ni, W.; Jiang, M.; Ruan, H. B.; Li, M. D.; Zhang, K.; Ding, Z.; Lee, P.; Singh, K.; Wu, J.; Herzog, R. I.; Kaech, S.; Wendel, H. G.; Yates, J. R. 3rd; Han, W.; Sherwin, R. S.; Nie, Y.; Yang, X. |
| Article Title: | O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth |
| Abstract: | Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined. O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities. Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2). PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability. Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT). O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth. These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis. © 2019, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; protein targeting; enzyme activity; proteomics; microarray analysis; upregulation; catalysis; tumor growth; genetic database; acylation; n acetylglucosamine; aerobic glycolysis; pyruvate kinase; pyruvate kinase m2; human; priority journal; article; hela cell line; acetylglucosaminidase; n acetylglucosamine transferase |
| Journal Title: | Oncogene |
| Volume: | 39 |
| Issue: | 3 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-01-16 |
| Start Page: | 560 |
| End Page: | 573 |
| Language: | English |
| DOI: | 10.1038/s41388-019-0975-3 |
| PUBMED: | 31501520 |
| PROVIDER: | scopus |
| PMCID: | PMC7107572 |
| DOI/URL: | |
| Notes: | Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work