The emerging role of the Nrf2–Keap1 signaling pathway in cancer
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Cites background from "The emerging role of the Nrf2–Keap1..."
...Specifically, NRF2 is activated following disruption of the interaction of NRF2 with its binding partner Kelch-like ECH-associated protein 1 (KEAP1)....
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...Critical cysteine residues within KEAP1 can undergo oxidation, succination, and glutathionylation, thereby inhibiting theKEAP1-NRF2 interaction, leading to the proteasomal degradation of NRF2....
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...Once activated, NRF2 induces the transcription of many antioxidant proteins including GPXs and TXNs as well as enzymes involved inGSHsynthesis and cysteine import through the cystine/ glutamate antiporter....
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...NRF2 also regulates the serine biosynthesis pathway, generating NADPH in the mitochondria, which is critical for redox balance under hypoxic conditions (129, 130)....
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...One mechanism by which cancer cells increase their antioxidant capacity is by activating the transcription factor nuclear factor (erythroidderived 2)–related factor-2 (NRF2) (127)....
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1,482 citations
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Cites background from "The emerging role of the Nrf2–Keap1..."
...Mutations of both these genes are observed in numerous cancers (Jaramillo and Zhang, 2013), and we would predict that these changes enhance AKR1C expression and possibly render cells resistant to the induction of ferroptosis downstream of system xc− inhibition....
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...Mutations of both these genes are observed in numerous cancers 684 (Jaramillo and Zhang, 2013) and we would predict that these changes enhance 685 AKR1C expression and possibly render cells resistant to the induction of 686 ferroptosis downstream of system xc inhibition....
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1,066 citations
Cites background from "The emerging role of the Nrf2–Keap1..."
...type and stage of the cancer.(7,8) For example, NRF2 prevents the initiation but accelerates the progression of chemical carcinogen-mediated or oncogene-mediated carcinogenesis....
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References
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"The emerging role of the Nrf2–Keap1..." refers background in this paper
...In the nucleus, Nrf2 dimerizes with members of the masculoaponeurotic fibrosarcoma (Maf) protein family that have been shown to facilitate the binding of Nrf2 to AREs located within the regulatory regions of a wide variety of genes involved in cytoprotection and metabolism (Itoh et al. 1997; Nguyen et al. 2000; Motohashi et al. 2004; Hirotsu et al. 2012)....
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...…fibrosarcoma (Maf) protein family that have been shown to facilitate the binding of Nrf2 to AREs located within the regulatory regions of a wide variety of genes involved in cytoprotection and metabolism (Itoh et al. 1997; Nguyen et al. 2000; Motohashi et al. 2004; Hirotsu et al. 2012)....
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3,166 citations
"The emerging role of the Nrf2–Keap1..." refers background in this paper
...The Kelch/DGR domain is critical for maintaining the interaction between Nrf2 and Keap1 by interacting with the Neh2 domain of Nrf2 (Itoh et al. 1999; McMahon et al. 2004)....
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3,152 citations
3,066 citations
"The emerging role of the Nrf2–Keap1..." refers background in this paper
...Activation of the Nrf2 defense response has been shown to protect against neurodegenerative diseases, aging, diabetes, photo-oxidative stress, cardiovascular disease, inflammation, pulmonary fibrosis, acute pulmonary injury, and cancer (for review, see Motohashi and Yamamoto 2004; Jeong et al. 2006; Zhang 2006; Kensler et al. 2007; Lau et al. 2008)....
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...…to protect against neurodegenerative diseases, aging, diabetes, photo-oxidative stress, cardiovascular disease, inflammation, pulmonary fibrosis, acute pulmonary injury, and cancer (for review, see Motohashi and Yamamoto 2004; Jeong et al. 2006; Zhang 2006; Kensler et al. 2007; Lau et al. 2008)....
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