NFE2L2 binds the TKT gene

Stable Identifier
R-HSA-9761834
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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NFE2L2 binds the TKT gene
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The TKT gene encodes transketolase, an enzyme that catalyzes two reversible reactions in the non-oxidative branch of the pentose phosphate pathway (PPP). Both TKT reactions consume (or produce, depending on direction) intermediates that are shared between PPP and glycolysis, positioning TKT as a key regulator of carbon flux between alternate glucose metabolism pathways (reviewed in Ge et al, 2020).
Expression of a number of genes involved in the pentose phosphate pathway, including TKT, have been shown to be regulated by NFE2L2 downstream of KEAP1. NFE2L2 was initially characterized as a transcription factor involved in antioxidant response and maintenance of cellular redox balance but has also been shown to be a critical regulator of metabolic reprogramming, including during oncogenesis (reviewed in Baird and Yamamoto, 2020; Ge et al, 2020; Smolkova et al, 2020). NFE2L2 binds to antioxidant response (ARE) elements in the promoter of target genes as a heterodimer with a member of the small MAF family of proteins. NFE2L2 upregulates expression in response to NFE2L2 inducers and has been shown to bind directly to the TKT promoter by ChIP-seq (Thimmulappa et al, 2002; Wu et al, 2011; Mitsuishi et al, 2012; Tang et al, 2021; reviewed in 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
33859744 c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation

Chu, PY, Chen, HH, Lin, LM, Chang, JY, Lin, SF, Chen, YT, Liu, KJ, Huang, YW, Chuang, YJ, Kuo, CC, Tsai, FY, Fang, HL, Hsiao, JR, Jiang, SS, Tang, YC

Theranostics 2021
32284348 The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

Yamamoto, M, Baird, L

Mol Cell Biol 2020
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
31989830 Nuclear Factor Erythroid 2-Related Factor 2 in Regulating Cancer Metabolism

Leguina-Ruzzi, A, Bai, P, Smolková, K, Kovács, T, Sipos, A, Mikó, E

Antioxid Redox Signal 2020
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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Authored
Rothfels, K  (2021-10-08)
Reviewed
Cuadrado, A  (2022-02-23)
Created
Rothfels, K  (2022-01-15)
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