NFE2L2-dependent PGD gene expression

Stable Identifier
R-HSA-9761846
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
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NFE2L2-dependent PGD gene expression
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Phosphogluconate 6-dehydrogenase catalyzes the third step of the pentose phosphate pathway (PPP), 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).
PGD expression is regulated downstream of NFE2L2 through binding of the transcription factor to anti-oxidant response elements in the promoter (Thimmulappa et al, 2002; Wu et al, 2011; Ong et al, 2020; Mitsuishi et al, 2012; reviewed in Baird and Yamamoto, 2020). Knockdown of PGD expression reduced the proliferation and colony formation of HepG2 cells and also downregulated expression of NFE2L2, suggesting the existence of a positive feedback loop (Ong et al, 2020).
Literature References
PubMed ID Title Journal Year
32336239 The positive feedback loop between Nrf2 and phosphogluconate dehydrogenase stimulates proliferation and clonogenicity of human hepatoma cells

Ong, AJ, Saeidi, S, Chi, NHK, Kim, SJ, Kim, DH, Kim, SH, Park, SA, Cha, YN, Na, HK, Surh, YJ

Free Radic Res 2020
12234984 Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray

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

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

Wu, KC, Cui, JY, Klaassen, CD

Toxicol Sci 2011
32649885 Oxidative Stress in Cancer

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

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

Baird, L, Yamamoto, M

Mol Cell Biol 2020
22789539 Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming

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

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

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

Front Endocrinol (Lausanne) 2020
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
PGD gene:p-AcK NFE2L2:CREBBP,EP300:MAFG [nucleoplasm] (Homo sapiens)
Active Unit
p-NFE2L2 [nucleoplasm]
Authored
Rothfels, K  (2021-10-08)
Reviewed
Cuadrado, A  (2022-02-23)
Created
Rothfels, K  (2022-01-15)
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