AcK-NFE2L2- dependent NQO1 gene expression

Stable Identifier
R-HSA-9759186
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
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AcK-NFE2L2- dependent NQO1 gene expression
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NQO1 (NAD(P)H:Quinone acceptor oxidoreductase type1) catalyzes the two-electron reduction of quinones to hydroquinones (Faig et al, 2000). This reaction bypasses the one electron reduction of these substrates by P450 reductase, which generates reactive oxygen species (ROS) and consequent stress and damage (reviewed in Ross and Siegel, 2021). NQO1 expression is upregulated by NFE2L2, CHD6 and MAFK binding to the antioxidant response element (ARE) in the promoter in response to stimulus by phase II inducers (oxidative and electrophillic stressors) (Itoh et al, 1997; McMahon et al, 2001; Nioi et al, 2005). These inducers activate the NFE2L2-KEAP1 pathway, stabilizing NFE2L2 and allowing it to enter the nucleus to activate expression of target genes (reviewed in Baird and Yamamoto, 2000)
Literature References
PubMed ID Title Journal Year
11309284 The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes

McMahon, M, Itoh, K, Yamamoto, M, Chanas, SA, Henderson, CJ, McLellan, LI, Wolf, CR, Cavin, C, Hayes, JD

Cancer Res 2001
9240432 An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements

Itoh, K, Chiba, T, Takahashi, S, Ishii, T, Igarashi, K, Katoh, Y, Oyake, T, Hayashi, N, Satoh, K, Hatayama, I, Yamamoto, M, Nabeshima, Y

Biochem Biophys Res Commun 1997
32284348 The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

Baird, L, Yamamoto, M

Mol Cell Biol 2020
10706635 Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release

Faig, M, Bianchet, MA, Talalay, P, Chen, S, Winski, S, Ross, D, Amzel, LM

Proc Natl Acad Sci U S A 2000
33774477 The diverse functionality of NQO1 and its roles in redox control

Ross, D, Siegel, D

Redox Biol 2021
16314513 The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation

Nioi, P, Nguyen, T, Sherratt, PJ, Pickett, CB

Mol Cell Biol 2005
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
NQO1 gene:p-AcK-NFE2L2:CHD6:MAFK [nucleoplasm] (Homo sapiens)
Active Unit
MAFK [nucleoplasm]
p-NFE2L2 [nucleoplasm]
Authored
Rothfels, K  (2021-10-08)
Reviewed
Cuadrado, A  (2022-02-23)
Created
Rothfels, K  (2021-11-29)
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