The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth
Open accessAbstract
The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked β-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for antioxidant defense. Blocking glycosylation of G6PD reduces cancer cell proliferation in vitro and impairs tumor growth in vivo. Importantly, G6PD glycosylation is increased in human lung cancers. Our findings reveal a mechanistic understanding of how O-glycosylation directly regulates the PPP to confer a selective growth advantage to tumours.
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Cites
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Cited by
Protein O-GlcNAcylation: emerging mechanisms and functions
Yang, X., & Qian, K. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.22 · Cited by 1,194
Oxygen availability and metabolic adaptations
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The Role of the Pentose Phosphate Pathway in Diabetes and Cancer
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Self-citationLiver glucose metabolism in humans
Adeva-Andany, M. M., Pérez-Felpete, N., Fernández-Fernández, C., Donapetry-García, C., & Pazos-García, C. (2016) · Bioscience Reports · doi:10.1042/bsr20160385 · Cited by 372
O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth
Nie, H., Ju, H., Fan, J., Shi, X., Cheng, Y., Cang, X., Zheng, Z., Duan, X., & Yi, W. (2020) · Nature Communications · doi:10.1038/s41467-019-13601-8 · Cited by 346
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Metadata
- Authors
- Rao, X., Duan, X., Mao, W., Li, X., Li, Z., Li, Q., Zheng, Z., Xu, H., Chen, M., Wang, P. G., Wang, Y., Shen, B., & Yi, W.
- Venue
- Nature Communications
- Published
- 2015-09-24
- Volume
- 6
- Issue
- 1
- Pages
- 8468-8468
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1766114318
- Cited by
- 257
- References
- 37
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- gold
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- Rao, X., Duan, X., Mao, W., Li, X., Li, Z., Li, Q., Zheng, Z., Xu, H., Chen, M., Wang, P. G., Wang, Y., Shen, B., & Yi, W. (2015). O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth. Nature Communications. https://doi.org/10.1038/ncomms9468
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