{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNuclear factor erythroid 2–related factor 2 (Nrf2) is a master redox‐sensitive transcription factor that orchestrates cellular defense against oxidative and electrophilic stress by inducing a wide array of cytoprotective genes. Under normal conditions, Nrf2 is sequestered in the cytoplasm by its inhibitor Keap1, which targets it for ubiquitin‑mediated proteasomal degradation. In response to cellular stress, electrophilic modification of Keap1 and other post‐translational events (such as phosphorylation and acetylation) permit Nrf2 stabilization and nuclear translocation, where it binds to antioxidant response elements (AREs) and promotes the transcription of detoxification, phase II metabolism, and antioxidant genes to reestablish redox homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in mediating antioxidant and detoxification responses, Nrf2 integrates signals from diverse cellular pathways to influence metabolism, autophagy, and cell survival. Interactions with adaptor proteins (such as p62) and regulatory kinases like glycogen synthase kinase‑3β and AMP‑activated protein kinase modulate its nuclear localization and transcriptional output. These mechanisms, which also affect metabolic reprogramming (including regulation of serine/glycine biosynthesis) and drug efflux, contribute to chemoresistance and enhanced cellular proliferation when Nrf2 is aberrantly activated—in many cancers, for instance, constitutive Nrf2 activity confers resistance to apoptosis and promotes tumor growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe dualistic nature of Nrf2 presents significant therapeutic implications. While activation of the Nrf2 pathway can protect normal tissues from oxidative injury, inflammation, and metabolic dysfunction (as in diabetic nephropathy and other chronic conditions), its persistent or deregulated activation in cancer cells can drive chemoresistance, metastasis, and even alter cell fate decisions such as ferroptosis. Emerging strategies aim either to inhibit Nrf2 in tumors to overcome drug resistance or to activate it in degenerative and age‐related diseases—in conditions as diverse as progeria and cardiac insulin resistance—to restore cellular homeostasis. This fine balance underscores the broad impact of Nrf2 on human health and the promise of targeted interventions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Truyen Nguyen, Philip J Sherratt, H-C Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26 S proteasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207293200"}], "href": "https://doi.org/10.1074/jbc.M207293200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12446695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12446695"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David A Bloom, Anil K Jaiswal "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element-mediated NAD(P)H:quinone oxidoreductase-1 gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307633200"}], "href": "https://doi.org/10.1074/jbc.M307633200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12947090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12947090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akira Kobayashi, Moon-Il Kang, Hiromi Okawa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00651.2005"}], "href": "https://doi.org/10.1152/ajpheart.00651.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16339837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16339837"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Balasundaram Padmanabhan, Kit I Tong, Tsutomu Ohta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2006.01.013"}], "href": "https://doi.org/10.1016/j.molcel.2006.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16507366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16507366"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Anju Singh, Vikas Misra, Rajesh K Thimmulappa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-5003"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-5003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18316592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18316592"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiao-Jun Wang, Zheng Sun, Nicole F Villeneuve, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgn095"}], "href": "https://doi.org/10.1093/carcin/bgn095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18413364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18413364"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Anju Singh, Swetlana Boldin-Adamsky, Rajesh K Thimmulappa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-1401"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-1401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18829555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18829555"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Alexandria Lau, Nicole F Villeneuve, Zheng Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dual roles of Nrf2 in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacol Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.phrs.2008.09.003"}], "href": "https://doi.org/10.1016/j.phrs.2008.09.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18838122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18838122"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Truyen Nguyen, Paul Nioi, Cecil B Pickett "}, {"type": "b", "children": [{"type": "t", "text": "The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.R900010200"}], "href": "https://doi.org/10.1074/jbc.R900010200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19182219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19182219"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Zheng Sun, Y Eugene Chin, Donna D Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01639-08"}], "href": "https://doi.org/10.1128/MCB.01639-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19273602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19273602"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "John D Hayes, Michael McMahon "}, {"type": "b", "children": [{"type": "t", "text": "NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Biochem Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tibs.2008.12.008"}], "href": "https://doi.org/10.1016/j.tibs.2008.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19321346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19321346"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yoo Ri Kim, Ji Eun Oh, Min Sung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.2653"}], "href": "https://doi.org/10.1002/path.2653"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19967722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19967722"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Tao Jiang, Zheping Huang, Yifeng Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db09-1342"}], "href": "https://doi.org/10.2337/db09-1342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20103708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20103708"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Alexandria Lau, Xiao-Jun Wang, Fei Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00248-10"}], "href": "https://doi.org/10.1128/MCB.00248-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20421418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20421418"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Ashish Jain, Trond Lamark, Eva Sjøttem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.118976"}], "href": "https://doi.org/10.1074/jbc.M110.118976"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20452972"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20452972"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Luisa M Solis, Carmen Behrens, Wenli Dong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-09-3352"}], "href": "https://doi.org/10.1158/1078-0432.CCR-09-3352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534738"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Dongmei Ren, Nicole F Villeneuve, Tao Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1014275108"}], "href": "https://doi.org/10.1073/pnas.1014275108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21205897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21205897"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Keiko Taguchi, Hozumi Motohashi, Masayuki Yamamoto "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2443.2010.01473.x"}], "href": "https://doi.org/10.1111/j.1365-2443.2010.01473.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21251164"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21251164"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Yi Tan, Tomonaga Ichikawa, Jinqing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db10-1164"}], "href": "https://doi.org/10.2337/db10-1164"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21270272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21270272"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Yoshihiro Inami, Satoshi Waguri, Ayako Sakamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201102031"}], "href": "https://doi.org/10.1083/jcb.201102031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21482715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21482715"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Gina M DeNicola, Florian A Karreth, Timothy J Humpton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10189"}], "href": "https://doi.org/10.1038/nature10189"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21734707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21734707"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "S Chowdhry, Y Zhang, M McMahon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.388"}], "href": "https://doi.org/10.1038/onc.2012.388"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22964642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22964642"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Suryakant K Niture, Raju Khatri, Anil K Jaiswal "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Nrf2-an update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2013.02.008"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2013.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23434765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23434765"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Louise Hecker, Naomi J Logsdon, Deepali Kurundkar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.3008182"}], "href": "https://doi.org/10.1126/scitranslmed.3008182"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24718857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24718857"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Cristina Espinosa-Diez, Verónica Miguel, Daniela Mennerich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antioxidant responses and cellular adjustments to oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2015.07.008"}], "href": "https://doi.org/10.1016/j.redox.2015.07.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26233704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26233704"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Ying Huang, Wenji Li, Zheng-yuan Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The complexity of the Nrf2 pathway: beyond the antioxidant response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jnutbio.2015.08.001"}], "href": "https://doi.org/10.1016/j.jnutbio.2015.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26419687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26419687"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Gina M DeNicola, Pei-Hsuan Chen, Edouard Mullarky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NRF2 regulates serine biosynthesis in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3421"}], "href": "https://doi.org/10.1038/ng.3421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26482881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26482881"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Joanna D Wardyn, Amy H Ponsford, Christopher M Sanderson "}, {"type": "b", "children": [{"type": "t", "text": "Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20150014"}], "href": "https://doi.org/10.1042/BST20150014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26551702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26551702"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Min Sung Joo, Won Dong Kim, Ki Young Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00118-16"}], "href": "https://doi.org/10.1128/MCB.00118-16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27161318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27161318"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Nard Kubben, Weiqi Zhang, Lixia Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Repression of the Antioxidant NRF2 Pathway in Premature Aging."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.05.017"}], "href": "https://doi.org/10.1016/j.cell.2016.05.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27259148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27259148"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Silvia Menegon, Amedeo Columbano, Silvia Giordano "}, {"type": "b", "children": [{"type": "t", "text": "The Dual Roles of NRF2 in Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Mol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmed.2016.05.002"}], "href": "https://doi.org/10.1016/j.molmed.2016.05.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27263465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27263465"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Claudia Tonelli, Iok In Christine Chio, David A Tuveson "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional Regulation by Nrf2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2017.7342"}], "href": "https://doi.org/10.1089/ars.2017.7342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28899199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28899199"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Ilaria Bellezza, Ileana Giambanco, Alba Minelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2-Keap1 signaling in oxidative and reductive stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2018.02.010"}], "href": "https://doi.org/10.1016/j.bbamcr.2018.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29499228"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29499228"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Masayuki Yamamoto, Thomas W Kensler, Hozumi Motohashi "}, {"type": "b", "children": [{"type": "t", "text": "The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Rev (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physrev.00023.2017"}], "href": "https://doi.org/10.1152/physrev.00023.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29717933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29717933"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Daiha Shin, Eun Hye Kim, Jaewang Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2018.10.426"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2018.10.426"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30339884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30339884"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Luca Lignitto, Sarah E LeBoeuf, Harrison Homer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2019.06.003"}], "href": "https://doi.org/10.1016/j.cell.2019.06.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31257023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31257023"}]}]}]}