AcK-NFE2L2-dependent P6GD gene expression

Stable Identifier
R-HSA-9761849
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first, rate limiting step of the pentose phosphate pathway (PPP). The PPP is an alternate glucose metabolic pathway that shares intermediates with glycolysis. PPP generates NADPH through its oxidative and non-oxidative branches, as well as biosynthetic intermediates required for the generation of nucleic acids, sterols, fatty acids and amino acids. Cells can switch to the PPP pathway in place of glycolysis and oxidative phosphorylation in times of high biosynthetic need, like proliferation, and also in response to oxidative stress, as the NADPH generated contributes to the redox potential of the cell (reviewed in Ge et al, 2020; Hayes et al, 2020; Baird and Yamamoto, 2020).
G6PD expression is regulated downstream of the KEAP1-NFE2L2 pathway and depends on the binding of an NFE2L2:MAFG heterodimer to the antioxidant response element in the promoter (Hirotsu et al, 2012; Mitsuishi et al, 2012; Thimmulappa et al, 2002; Wu et al, 2011; reviewed in Baird and Yamamoto, 2020; Ge et al, 2020).
Literature References
PubMed ID Title Journal Year
12234984 Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray

Yamamoto, M, Srisuma, S, Mai, KH, Biswal, S, Thimmulappa, RK, Kensler, TW

Cancer Res 2002
21775727 Beneficial role of Nrf2 in regulating NADPH generation and consumption

Klaassen, CD, Wu, KC, Cui, JY

Toxicol Sci 2011
32649885 Oxidative Stress in Cancer

Hayes, JD, Tew, KD, Dinkova-Kostova, AT

Cancer Cell 2020
32284348 The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

Yamamoto, M, Baird, L

Mol Cell Biol 2020
22965115 Nrf2-MafG heterodimers contribute globally to antioxidant and metabolic networks

Nagashima, T, Yamamoto, M, Hirotsu, Y, Engel, JD, Funayama, R, Katsuoka, F, Nakayama, K, Nishida, Y

Nucleic Acids Res 2012
22789539 Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming

Motohashi, H, Yamamoto, M, Nukiwa, T, Aburatani, H, Kawatani, Y, Shibata, T, Mitsuishi, Y, Taguchi, K

Cancer Cell 2012
32582032 The Role of the Pentose Phosphate Pathway in Diabetes and Cancer

Ge, T, Yang, J, Tong, X, Wang, Y, Zhou, S, Li, Y

Front Endocrinol (Lausanne) 2020
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