AcK-NFE2L2-dependent GCLM gene expression

Stable Identifier
R-HSA-9760125
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
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AcK-NFE2L2-dependent GCLM gene expression
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The GCLM gene encodes the regulatory subunit of glutamate-cysteine ligase, an enzyme that ligates glutamate and cysteine as one step in the synthesis of glutathione. Glutathione contributes to the antioxidant response by reducing peroxides, neutralizing and promoting the export of xenobiotic agents and by acting as a redox buffer (reviewed in Lu, 2013). Expression of GCLM is dependent in part on the binding of NFE2L2 to the antioxidant response element (ARE) in the promoter (Sekhar et al, 2000; McMahon et al, 2001; Thimmulappa et al, 2002). Binding and transcription factor activity are enhanced by previous NFE2L2 acetylation mediated by CREBBP or EP300 (Sun et al, 2009).
Literature References
PubMed ID Title Journal Year
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
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
22995213 Glutathione synthesis

Lu, SC

Biochim Biophys Acta 2013
10733945 Inhibition of the 26S proteasome induces expression of GLCLC, the catalytic subunit for gamma-glutamylcysteine synthetase

Sekhar, KR, Soltaninassab, SR, Borrelli, MJ, Xu, ZQ, Meredith, MJ, Domann, FE, Freeman, ML

Biochem Biophys Res Commun 2000
19273602 Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response

Sun, Z, Chin, YE, Zhang, DD

Mol Cell Biol 2009
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
GCLM gene:p-AcK-NFE2L2:CREBBP, EP300 [nucleoplasm] (Homo sapiens)
Active Unit
p-AcK-NFE2L2:CREBBP, EP300 [nucleoplasm]
Authored
Rothfels, K  (2021-10-08)
Reviewed
Cuadrado, A  (2022-02-23)
Created
Rothfels, K  (2021-12-14)
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