AcK-NFE2L2 and ATF4 bind the SLC7A11 gene

Stable Identifier
R-HSA-9761815
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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AcK-NFE2L2 and ATF4 bind the SLC7A11 gene
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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). NFE2L2 is a major transcriptional regulator of genes involved in mitigating oxidative stress, and as such effectively acts as a negative regulator of the ferroptosis pathway (reviewed in Baird and Yamamoto, 2020; Kuang et al, 2020; Chen et al, 2021). SLC7A11 expression is upregulated in response to NFE2L2 inducers and has been shown to be a direct downstream target of NFE2L2 and ATF4 (Ye et al, 2014; Ishii et al, 2000; Sasaki et al, 2002; Chen et al, 2017; Dong et al, 2020; reviewed in Kuang et al, 2020; Kajarabille and Latunde-Dada, 2019). CREBBP also co-immunoprecipitates with NFE2L2 at the SLC7A11, and CREBBP-dependent acetylation of NFE2L2 is required for promoter binding and transcriptional activation (Chen et al, 2017; Sun et al, 2009). The acetylation activity of CREBBP is inhibited by interaction between p14ARF and NFE2L2 at the SLC7A11 promoter (Chen et al, 2017).
Literature References
PubMed ID Title Journal Year
28985506 NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression

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

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

Kajarabille, N, Latunde-Dada, GO

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

Baird, L, Yamamoto, M

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Mol Cell Biol 2014
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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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