AcK-NFE2L2-dependent SLC7A11 expression

Stable Identifier
R-HSA-9761841
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, plasma membrane
ReviewStatus
5/5
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AcK-NFE2L2-dependent SLC7A11 expression
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SLC7A11 encodes one component of system xc-, a heterodimeric high affinity cystine-glutamate transporter that imports cystine in exchange for glutamate; the other protein component of the heterodimer is SLC3A2 (reviewed in Lewerenz et al, 2013). System xc- contributes to redox balance of the cell by increasing intracellular stores of cysteine, a limiting component in the synthesis of the key antioxidant glutathione (GSH). Depletion of GSH, for instance by inhibition of SLC7A11, causes lipid peroxidation and stimulates ferroptosis, a regulated form of cell death (reiewed in Chen et al, 2021; Kuang et al, 2020; Kajarabille and Latunde-Dada, 2019). Expression of SLC7A11 is regulated downstream of the KEAP1:NFE2L2 pathway in response to oxidative stress. NFE2L2 and SLC7A11 are therefore both negative regulators of ferroptosis (Ye et al, 2014; Ishii et al, 2000; Sasaki et al, 2002; Chen et al, 2017; Dong et al, 2020; reviewed in Baird and Yamamoto, 2020; Kuang et al, 2020; Chen et al, 2021).
Literature References
PubMed ID Title Journal Year
28985506 NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression

Baer, R, Gu, W, Erber, L, Chen, Y, Tavana, O, Chu, B, Chen, D

Mol Cell 2017
31597407 Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators

Latunde-Dada, GO, Kajarabille, N

Int J Mol Sci 2019
32284348 The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

Yamamoto, M, Baird, L

Mol Cell Biol 2020
22667998 The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities

Ganapathy, V, Smolders, I, Maher, P, Kalivas, PW, Lambros, M, Smith, SB, Pergande, M, Lewerenz, J, Methner, A, Gout, PW, Massie, A, Hewett, SJ, Huang, Y

Antioxid Redox Signal 2013
12235164 Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression

Wang, H, Yamamoto, M, Maebara, K, Tamba, M, Itoh, K, Sato, H, Sato, K, Kuriyama-Matsumura, K, Bannai, S, Sasaki, H

J Biol Chem 2002
10821856 Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages

Ishii, T, Sato, H, Yamamoto, M, Takahashi, S, Yanagawa, T, Bannai, S, Itoh, K, Katoh, Y

J Biol Chem 2000
33043019 Oxidative Damage and Antioxidant Defense in Ferroptosis

Tang, D, Liu, J, Kang, R, Kuang, F

Front Cell Dev Biol 2020
32601262 Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1

Xia, Y, Hu, R, Chai, D, Peng, J, Dong, H, Qiang, Z, Jiang, H

Aging (Albany NY) 2020
33462411 Cellular degradation systems in ferroptosis

Yu, C, Chen, X, Tang, D, Kroemer, G, Kang, R

Cell Death Differ 2021
25002527 Nrf2- and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition

Okada, T, Ohyama, C, Itoh, K, Mimura, J, Ye, P, Liu, T, Sato, H, Maruyama, A

Mol Cell Biol 2014
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
SLC7A11 gene:p-AcK-NFE2L2:ATF4 [nucleoplasm] (Homo sapiens)
Active Unit
ATF4 [nucleoplasm]
p-AcK-NFE2L2:CREBBP, EP300 [nucleoplasm]
Authored
Rothfels, K  (2021-10-08)
Reviewed
Cuadrado, A  (2022-02-23)
Created
Rothfels, K  (2022-01-15)
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