NFE2L2

Summary

Gene Symbol: NFE2L2
Description: nuclear factor, erythroid 2 like 2
Alias: HEBP1, IMDDHH, NRF2, nuclear factor erythroid 2-related factor 2, nuclear factor erythroid-derived 2-like 2
Species: human
Products:     NFE2L2

Top Publications

  1. Malec V, Gottschald O, Li S, Rose F, Seeger W, Hänze J. HIF-1 alpha signaling is augmented during intermittent hypoxia by induction of the Nrf2 pathway in NOX1-expressing adenocarcinoma A549 cells. Free Radic Biol Med. 2010;48:1626-35 pubmed publisher
    ..affect the regulation of hypoxia-inducible factor (HIF-1) and the nuclear factor erythroid 2-related factor 2 (Nrf2). HIF-1 is primarily induced in hypoxia, whereas Nrf2 is induced in response to oxidative stress...
  2. MacLeod A, McMahon M, Plummer S, Higgins L, Penning T, Igarashi K, et al. Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compo. Carcinogenesis. 2009;30:1571-80 pubmed publisher
    ..7-fold. Activation of NRF2, by KEAP1 knockdown, caused a 75% increase in the amount of glutathione in HaCaT cells and a 1.4- to 1...
  3. Singh A, Wu H, Zhang P, Happel C, Ma J, Biswal S. Expression of ABCG2 (BCRP) is regulated by Nrf2 in cancer cells that confers side population and chemoresistance phenotype. Mol Cancer Ther. 2010;9:2365-76 pubmed publisher
    ..b>Nrf2, a redox-sensing transcription factor, on constitutive activation in non-small-cell lung cancer cells upregulates a ..
  4. Singh A, Happel C, Manna S, Acquaah Mensah G, Carrerero J, Kumar S, et al. Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. J Clin Invest. 2013;123:2921-34 pubmed publisher
    The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood...
  5. Dayoub R, Vogel A, Schuett J, Lupke M, Spieker S, Kettern N, et al. Nrf2 activates augmenter of liver regeneration (ALR) via antioxidant response element and links oxidative stress to liver regeneration. Mol Med. 2013;19:237-44 pubmed publisher
    ..can be impaired by permanent oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2), known to regulate the cellular antioxidant response, and has been shown to improve the process of liver ..
  6. Kweider N, Fragoulis A, Rosen C, Pecks U, Rath W, Pufe T, et al. Interplay between vascular endothelial growth factor (VEGF) and nuclear factor erythroid 2-related factor-2 (Nrf2): implications for preeclampsia. J Biol Chem. 2011;286:42863-72 pubmed publisher
    ..Here, we show that VEGF activated Nrf2, the main regulating factor of the intracellular redox balance, in the cytotrophic cell line BeWo...
  7. Ganan Gomez I, Wei Y, Yang H, Boyano Adánez M, Garcia Manero G. Oncogenic functions of the transcription factor Nrf2. Free Radic Biol Med. 2013;65:750-764 pubmed publisher
    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that controls the expression of a large pool of antioxidant and cytoprotective genes regulating the cellular response to oxidative and electrophilic stress...
  8. Ma J, Cai H, Wu T, Sobhian B, Huo Y, Alcivar A, et al. PALB2 interacts with KEAP1 to promote NRF2 nuclear accumulation and function. Mol Cell Biol. 2012;32:1506-17 pubmed publisher
    ..with KEAP1, an oxidative stress sensor that binds and represses the master antioxidant transcription factor NRF2. PALB2 shares with NRF2 a highly conserved ETGE-type KEAP1 binding motif and can effectively compete with NRF2 for ..
  9. Duong H, Yi Y, Kang H, Hong Y, Tang W, Wang A, et al. Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol. 2014;44:959-69 pubmed publisher
    ..The effect of PIK-75 on the level and activity of NRF2 was characterized using various assays including reporter gene, quantitative PCR, DNA-binding and western blot ..

More Information

Publications215 found, 100 shown here

  1. Ji X, Wang H, Zhu J, Zhu L, Pan H, Li W, et al. Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1?. Int J Cancer. 2014;135:574-84 pubmed publisher
    ..increasingly raised that several types of cancers overexpressed the nuclear factor erythroid 2-related factor 2 (Nrf2), which contributed strikingly to cancer biological capabilities and chemoresistance...
  2. Huang C, Zhang L, Ma S, Zhao Z, Wang W, He K, et al. Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma. PLoS ONE. 2013;8:e83479 pubmed publisher
    ..However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC) has not been elucidated...
  3. Zucker S, Fink E, Bagati A, Mannava S, Bianchi Smiraglia A, Bogner P, et al. Nrf2 amplifies oxidative stress via induction of Klf9. Mol Cell. 2014;53:916-928 pubmed publisher
    Reactive oxygen species (ROS) activate NF-E2-related transcription factor 2 (Nrf2), a key transcriptional regulator driving antioxidant gene expression and protection from oxidant injury...
  4. Kang K, Piao M, Kim K, Kang H, Chang W, Park I, et al. Epigenetic modification of Nrf2 in 5-fluorouracil-resistant colon cancer cells: involvement of TET-dependent DNA demethylation. Cell Death Dis. 2014;5:e1183 pubmed publisher
    ..Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional regulator and a possible target to overcome 5-FU resistance...
  5. Bao L, Jaramillo M, Zhang Z, Zheng Y, Yao M, Zhang D, et al. Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma. Int J Clin Exp Pathol. 2014;7:1502-13 pubmed
    Cisplatin resistance is a major problem affecting ovarian carcinoma treatment. NF-E2-related factor 2 (Nrf2), a nuclear transcription factor, plays an important role in chemotherapy resistance...
  6. Shimoyama Y, Mitsuda Y, Tsuruta Y, Hamajima N, Niwa T. Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure and cardiovascular mortality in hemodialysis patients. Int J Med Sci. 2014;11:726-31 pubmed publisher
    b>Nrf2 is a transcription factor that regulates the expression of antioxidant genes...
  7. Paul M, Bisht B, Darmawan D, Chiou R, Ha V, Wallace W, et al. Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling. Cell Stem Cell. 2014;15:199-214 pubmed publisher
    ..Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges ..
  8. Gjyshi O, Bottero V, Veettil M, Dutta S, Singh V, Chikoti L, et al. Kaposi's sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathog. 2014;10:e1004460 pubmed publisher
    ..One of the downstream targets of ROS is nuclear factor E2-related factor 2 (Nrf2), a transcription factor with important anti-oxidative functions...
  9. von Otter M, Landgren S, Nilsson S, Celojevic D, Bergström P, Håkansson A, et al. Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease. BMC Med Genet. 2010;11:36 pubmed publisher
    ..Here, we hypothesize that variation in NFE2L2 and KEAP1, the genes encoding the two major regulators of the phase II response, may affect the risk of Parkinson'..
  10. You A, Nam C, Wakabayashi N, Yamamoto M, Kensler T, Kwak M. Transcription factor Nrf2 maintains the basal expression of Mdm2: An implication of the regulation of p53 signaling by Nrf2. Arch Biochem Biophys. 2011;507:356-64 pubmed publisher
    ..This notion raises a possibility that NF-E2-related factor 2 (Nrf2), which confers cytoprotection against oxidative stress, and p53 can have a direct co-regulation network...
  11. Yang Y, Lii C, Wei Y, Li C, Lu C, Liu K, et al. Docosahexaenoic acid inhibition of inflammation is partially via cross-talk between Nrf2/heme oxygenase 1 and IKK/NF-?B pathways. J Nutr Biochem. 2013;24:204-12 pubmed publisher
    ..increased the protein expression of heme oxygenase 1 (HO-1), induced nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus and up-regulated antioxidant response element (ARE)-luciferase reporter activity...
  12. Lo S, Hannink M. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. Exp Cell Res. 2008;314:1789-803 pubmed publisher
    ..Mitochondria are a major source of ROS, while many anti-oxidant genes are regulated by the Nrf2 transcription factor...
  13. Seng S, Avraham H, Birrane G, Jiang S, Li H, Katz G, et al. NRP/B mutations impair Nrf2-dependent NQO1 induction in human primary brain tumors. Oncogene. 2009;28:378-89 pubmed publisher
    ..protein nuclear restricted protein in brain (NRP/B) was colocalized and interacted with NF-E2-related factor 2 (Nrf2)...
  14. Eggler A, Liu G, Pezzuto J, van Breemen R, Mesecar A. Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc Natl Acad Sci U S A. 2005;102:10070-5 pubmed
    ..sensor protein Kelch-like ECH-associated protein 1 (Keap1) and the transcription factor NF-E2-related factor 2 (Nrf2). Under basal conditions, Keap1 sequesters Nrf2 in the cytoplasm by binding to its Neh2 domain...
  15. Cook A, Vitale A, Ravishankar S, Matigian N, Sutherland G, Shan J, et al. NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's disease. PLoS ONE. 2011;6:e21907 pubmed publisher
    ..Transcriptomic analysis of Patient and Control hONS cells identified the NRF2 transcription factor signalling pathway as the most differentially expressed in Parkinson's disease...
  16. Wang X, Sun Z, Chen W, Li Y, Villeneuve N, Zhang D. Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction. Toxicol Appl Pharmacol. 2008;230:383-9 pubmed publisher
    ..Previously, we reported that activation of the Nrf2-mediated cellular defense pathway confers protection against toxic effects induced by sodium arsenite [As(III)] or ..
  17. Wruck C, Huppertz B, Bose P, Brandenburg L, Pufe T, Kadyrov M. Role of a fetal defence mechanism against oxidative stress in the aetiology of preeclampsia. Histopathology. 2009;55:102-6 pubmed publisher
    ..against oxidative stress and, in particular, the specific role of nuclear factor erythroid 2-related factor 2 (Nrf2)...
  18. Huang H, Nguyen T, Pickett C. Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proc Natl Acad Sci U S A. 2000;97:12475-80 pubmed
    ..NF-E2-related factor 2 (Nrf2), a member of the Cap'n'Collar family of basic region-leucine zipper (bZIP) transcription factors, has been ..
  19. Hartikainen J, Tengström M, Kosma V, Kinnula V, Mannermaa A, Soini Y. Genetic polymorphisms and protein expression of NRF2 and Sulfiredoxin predict survival outcomes in breast cancer. Cancer Res. 2012;72:5537-46 pubmed publisher
    b>NRF2 activates several protective genes, such as sulfiredoxin (SRXN1), as a response to oxidative and xenobiotic stress. Defects in NRF2 pathway may increase cancer susceptibility...
  20. Li W, Yu S, Kong A. Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain. J Biol Chem. 2006;281:27251-63 pubmed
    NF-E2-related factor 2 (Nrf2) is the key transcription factor regulating the antioxidant response...
  21. Ohta T, Iijima K, Miyamoto M, Nakahara I, Tanaka H, Ohtsuji M, et al. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 2008;68:1303-9 pubmed publisher
    Oxidative and electrophilic stresses are sensed by Keap1, which activates Nrf2 to achieve cytoprotection by regulating the expression of drug-metabolizing and antioxidative stress enzymes/proteins...
  22. Jiang T, Huang Z, Chan J, Zhang D. Nrf2 protects against As(III)-induced damage in mouse liver and bladder. Toxicol Appl Pharmacol. 2009;240:8-14 pubmed publisher
    ..Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is ..
  23. Fourquet S, Guerois R, Biard D, Toledano M. Activation of NRF2 by nitrosative agents and H2O2 involves KEAP1 disulfide formation. J Biol Chem. 2010;285:8463-71 pubmed publisher
    The NRF2 transcription factor regulates a major environmental and oxidative stress response...
  24. Shibata T, Kokubu A, Gotoh M, Ojima H, Ohta T, Yamamoto M, et al. Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology. 2008;135:1358-1368, 1368.e1-4 pubmed publisher
    ..We attempted to examine whether deregulation of Nrf2, a master transcriptional factor of various cytoprotective genes against oxidative stress, plays a role in the ..
  25. Nioi P, Nguyen T. A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity. Biochem Biophys Res Commun. 2007;362:816-21 pubmed
    ..Its primary role is to catalyze the ubiquitylation of the Nrf2 transcription factor...
  26. Liu G, Qu J, Shen X. NF-kappaB/p65 antagonizes Nrf2-ARE pathway by depriving CBP from Nrf2 and facilitating recruitment of HDAC3 to MafK. Biochim Biophys Acta. 2008;1783:713-27 pubmed publisher
    ..with anti-inflammatory or anti-tumor signaling pathway? Here, we report that NF-kappaB p65 subunit repressed the Nrf2-antioxidant response element (ARE) pathway at transcriptional level...
  27. Cullinan S, Gordan J, Jin J, Harper J, Diehl J. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol Cell Biol. 2004;24:8477-86 pubmed
    The Nrf2 transcription factor promotes survival following cellular insults that trigger oxidative damage. Nrf2 activity is opposed by the BTB/POZ domain protein Keap1...
  28. Rao V, Klein S, Bonar S, Zielonka J, Mizuno N, Dickey J, et al. The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer redox agent mitoquinone. J Biol Chem. 2010;285:34447-59 pubmed publisher
    ..Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells...
  29. Lee J, Koh K, Kim Y, Ahn J, Kim S. Upregulation of Nrf2 expression by human cytomegalovirus infection protects host cells from oxidative stress. J Gen Virol. 2013;94:1658-68 pubmed publisher
    NF-E2 related factor 2 (Nrf2) is a transcription factor that plays a key role(s) in cellular defence against oxidative stress...
  30. Gorrini C, Baniasadi P, Harris I, Silvester J, Inoue S, Snow B, et al. BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival. J Exp Med. 2013;210:1529-44 pubmed publisher
    ..Here, we show that BRCA1 regulates Nrf2-dependent antioxidant signaling by physically interacting with Nrf2 and promoting its stability and activation...
  31. Yu M, Li H, Liu Q, Liu F, Tang L, Li C, et al. Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway. Cell Signal. 2011;23:883-92 pubmed publisher
    Keap1 is an inhibitor of Nrf2 involved in Nrf2-dependent antioxidant response. However, the mechanisms on how Keap1 regulates Nrf2-ARE signaling pathway remains to be determined...
  32. Kwak M, Wakabayashi N, Itoh K, Motohashi H, Yamamoto M, Kensler T. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J Biol Chem. 2003;278:8135-45 pubmed
    ..putative molecular sensor for inducers is Keap1, a sulfhydryl-rich protein that sequesters the transcription factor Nrf2 in the cytoplasm...
  33. Hong F, Sekhar K, Freeman M, Liebler D. Specific patterns of electrophile adduction trigger Keap1 ubiquitination and Nrf2 activation. J Biol Chem. 2005;280:31768-75 pubmed
    Activation of the transcription factor Nrf2 regulates expression of phase II enzymes and other adaptive responses to electrophile and oxidant stress...
  34. Shibata T, Ohta T, Tong K, Kokubu A, Odogawa R, Tsuta K, et al. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A. 2008;105:13568-73 pubmed publisher
    The nuclear factor E2-related factor 2 (Nrf2) is a master transcriptional activator of genes encoding numerous cytoprotective enzymes that are induced in response to environmental and endogenously derived oxidative/electrophilic agents...
  35. Kobayashi A, Kang M, Okawa H, Ohtsuji M, Zenke Y, Chiba T, et al. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 2004;24:7130-9 pubmed
    Transcription factor Nrf2 is a major regulator of genes encoding phase 2 detoxifying enzymes and antioxidant stress proteins in response to electrophilic agents and oxidative stress...
  36. Nguyen T, Huang H, Pickett C. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem. 2000;275:15466-73 pubmed
    ..Recent studies using knockout mice suggest that NF-E2-related factor 2 (Nrf2), along with small Maf proteins, binds and activates the ARE...
  37. Stewart D, Killeen E, Naquin R, Alam S, Alam J. Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. J Biol Chem. 2003;278:2396-402 pubmed
    b>Nrf2 mediates inducer-dependent activation of the heme oxygenase-1 (HO-1) gene (Alam, J., Stewart, D., Touchard, C., Boinapally, S., Choi, A. M., and Cook, J. L. (1999) J. Biol. Chem...
  38. Dai G, Vaughn S, Zhang Y, Wang E, Garcia Cardena G, Gimbrone M. Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res. 2007;101:723-33 pubmed
    ..that atheroprotective flow upregulated certain antioxidant genes and strongly activated the transcription factor Nrf2. Using a strategy of small interfering RNA inhibition of Nrf2 expression combined with genome-wide transcriptional ..
  39. Volonte D, Liu Z, Musille P, Stoppani E, Wakabayashi N, Di Y, et al. Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence. Mol Biol Cell. 2013;24:1852-62 pubmed publisher
    ..The nuclear erythroid 2 p45-related factor-2 (Nrf2) is a transcription factor that mediates cytoprotective responses against stress...
  40. Dhakshinamoorthy S, Jain A, Bloom D, Jaiswal A. Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants. J Biol Chem. 2005;280:16891-900 pubmed
    The antioxidant response element (ARE) and Nrf2 are known to regulate the expression and coordinated induction of genes encoding detoxifying enzymes including NAD(P)H:quinone oxidoreductase1 (NQO1) in response to antioxidants...
  41. Lau A, Villeneuve N, Sun Z, Wong P, Zhang D. Dual roles of Nrf2 in cancer. Pharmacol Res. 2008;58:262-70 pubmed publisher
    In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing genes, including those encoding ..
  42. Paupe V, Dassa E, Goncalves S, Auchère F, Lönn M, Holmgren A, et al. Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS ONE. 2009;4:e4253 pubmed publisher
    ..patients with Friedreich ataxia exhibited hypersensitivity to oxidative insults because of an impairment in the Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes...
  43. Arlt A, Sebens S, Krebs S, Geismann C, Grossmann M, Kruse M, et al. Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity. Oncogene. 2013;32:4825-35 pubmed publisher
    Evidence accumulates that the transcription factor nuclear factor E2-related factor 2 (Nrf2) has an essential role in cancer development and chemoresistance, thus pointing to its potential as an anticancer target and undermining its ..
  44. Sun Z, Chin Y, Zhang D. Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol Cell Biol. 2009;29:2658-72 pubmed publisher
    ..b>Nrf2 is the critical transcription factor responsible for ARE-dependent transcription...
  45. Zhang D, Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol Cell Biol. 2003;23:8137-51 pubmed
    ..The bZIP transcription factor Nrf2 has emerged as a key regulator of this cancer-preventive genetic program...
  46. Konstantinopoulos P, Spentzos D, Fountzilas E, Francoeur N, Sanisetty S, Grammatikos A, et al. Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res. 2011;71:5081-9 pubmed publisher
    ..Because the cellular response to electrophilic xenobiotics is partly mediated by Keap1-Nrf2 pathway, we evaluated the presence of Kelch-like ECH-associated protein 1 (Keap1) mutations and NF-E2-related ..
  47. Baird L, Lleres D, Swift S, Dinkova Kostova A. Regulatory flexibility in the Nrf2-mediated stress response is conferred by conformational cycling of the Keap1-Nrf2 protein complex. Proc Natl Acad Sci U S A. 2013;110:15259-64 pubmed publisher
    The transcription factor NF-E2 p45-related factor 2 (Nrf2), a master regulator of cytoprotective genes, is controlled by dimeric Kelch-like ECH associated protein 1 (Keap1), a substrate adaptor protein for Cullin3/RING-box protein 1 ..
  48. Kwak M, Wakabayashi N, Greenlaw J, Yamamoto M, Kensler T. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway. Mol Cell Biol. 2003;23:8786-94 pubmed
    ..No induction was seen in mice where the transcription factor Nrf2 was disrupted...
  49. Yeh C, Yen G. Involvement of p38 MAPK and Nrf2 in phenolic acid-induced P-form phenol sulfotransferase expression in human hepatoma HepG2 cells. Carcinogenesis. 2006;27:1008-17 pubmed
    ..Moreover, gallic acid increased the nuclear levels of Nrf2, a transcription factor governing antioxidant response element (ARE)...
  50. Singh A, Boldin Adamsky S, Thimmulappa R, Rath S, Ashush H, Coulter J, et al. 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. Cancer Res. 2008;68:7975-84 pubmed publisher
    Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of electrophile and xenobiotic detoxification enzymes and efflux proteins, which confer cytoprotection against ..
  51. Natarajan V, Singh A, Kumar A, Sharma P, Kar H, Marrot L, et al. Transcriptional upregulation of Nrf2-dependent phase II detoxification genes in the involved epidermis of vitiligo vulgaris. J Invest Dermatol. 2010;130:2781-9 pubmed publisher
    ..In this study we show that the key transcription factor nuclear factor E2-related factor 2 (Nrf2) and the downstream genes NAD(P)H:quinone oxidase-1 (NQO-1), ?-glutamyl cystine ligase catalytic subunit (GCLC), ..
  52. Lo S, Li X, Henzl M, Beamer L, Hannink M. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. EMBO J. 2006;25:3605-17 pubmed
    Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels of Nrf2, a bZIP transcription factor, in response to oxidative stress...
  53. Zhang D. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 2006;38:769-89 pubmed
    ..cellular defense mechanisms against oxidative stress or electrophiles is mediated by the transcription factor Nrf2. Under the basal condition, Nrf2-dependent transcription is repressed by a negative regulator Keap1...
  54. Taguchi K, Fujikawa N, Komatsu M, Ishii T, Unno M, Akaike T, et al. Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc Natl Acad Sci U S A. 2012;109:13561-6 pubmed publisher
    The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system is essential for cytoprotection against oxidative and electrophilic insults...
  55. Chen X, Dodd G, Thomas S, Zhang X, Wasserman M, Rovin B, et al. Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression. Am J Physiol Heart Circ Physiol. 2006;290:H1862-70 pubmed
    ..NF-E2-related factor 2 (Nrf2) is a transcription factor that activates ARE-containing genes...
  56. Yamamoto T, Kyo M, Kamiya T, Tanaka T, Engel J, Motohashi H, et al. Predictive base substitution rules that determine the binding and transcriptional specificity of Maf recognition elements. Genes Cells. 2006;11:575-91 pubmed
    ..analyzed the binding of Maf-containing dimers to variant sequences of the MARE using bacterially expressed MafG and Nrf2 proteins and a surface plasmon resonance-microarray imaging technique...
  57. Wang X, Sun Z, Villeneuve N, Zhang S, Zhao F, Li Y, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 2008;29:1235-43 pubmed publisher
    ..Here, we report that inhibition of NF-E2-related factor 2 (Nrf2) may be a promising strategy to combat chemoresistance...
  58. Hsieh C, Hsiao H, Wu W, Liu C, Tsai Y, Chao Y, et al. Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells. J Biomed Sci. 2009;16:12 pubmed publisher
    ..Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes ..
  59. Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011;16:123-40 pubmed publisher
    The Keap1–Nrf2 regulatory pathway plays a central role in the protection of cells against oxidative and xenobiotic damage...
  60. Sun Z, Wu T, Zhao F, Lau A, Birch C, Zhang D. KPNA6 (Importin {alpha}7)-mediated nuclear import of Keap1 represses the Nrf2-dependent antioxidant response. Mol Cell Biol. 2011;31:1800-11 pubmed publisher
    The transcription factor Nrf2 has emerged as a master regulator of cellular redox homeostasis...
  61. Chen X, Varner S, Rao A, Grey J, Thomas S, Cook C, et al. Laminar flow induction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism. J Biol Chem. 2003;278:703-11 pubmed
    ..Expression of antisense Nrf2 (a transcriptional factor for ARE), a dominant negative Nrf2, or the cytoplasmic inhibitor of Nrf2 (Keap1/INrf2) ..
  62. McMahon M, Thomas N, Itoh K, Yamamoto M, Hayes J. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J Biol Chem. 2006;281:24756-68 pubmed
    ..The resulting complex facilitates ubiquitylation of the Nrf2 transcription factor but only when this substrate possesses within its Neh2 domain a second cryptic Keap1-binding ..
  63. Sun Z, Zhang S, Chan J, Zhang D. Keap1 controls postinduction repression of the Nrf2-mediated antioxidant response by escorting nuclear export of Nrf2. Mol Cell Biol. 2007;27:6334-49 pubmed
    The transcription factor Nrf2 regulates cellular redox homeostasis. Under basal conditions, Keap1 recruits Nrf2 into the Cul3-containing E3 ubiquitin ligase complex for ubiquitin conjugation and subsequent proteasomal degradation...
  64. Sun Z, Huang Z, Zhang D. Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response. PLoS ONE. 2009;4:e6588 pubmed publisher
    The bZIP transcription factor Nrf2 has emerged as a pivotal regulator of intracellular redox homeostasis by controlling the expression of many endogenous antioxidants and phase II detoxification enzymes...
  65. Boettler U, Volz N, Teller N, Haupt L, Bakuradze T, Eisenbrand G, et al. Induction of antioxidative Nrf2 gene transcription by coffee in humans: depending on genotype?. Mol Biol Rep. 2012;39:7155-62 pubmed publisher
    ..To date, nine single nucleotide polymorphisms (SNPs) have been identified in the Nrf2 (NFE2L2) gene...
  66. Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N, et al. Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res. 2009;15:3423-32 pubmed publisher
    NF-E2-related factor 2 (Nrf2), a key transcription regulator for antioxidant and detoxification enzymes, is abundantly expressed in cancer cells...
  67. Zhao F, Wu T, Lau A, Jiang T, Huang Z, Wang X, et al. Nrf2 promotes neuronal cell differentiation. Free Radic Biol Med. 2009;47:867-79 pubmed publisher
    The transcription factor Nrf2 has emerged as a master regulator of the endogenous antioxidant response, which is critical in defending cells against environmental insults and in maintaining intracellular redox balance...
  68. Shen G, Hebbar V, Nair S, Xu C, Li W, Lin W, et al. Regulation of Nrf2 transactivation domain activity. The differential effects of mitogen-activated protein kinase cascades and synergistic stimulatory effect of Raf and CREB-binding protein. J Biol Chem. 2004;279:23052-60 pubmed
    Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of Phase II detoxifying enzymes as well as anti-oxidative enzymes...
  69. Kim T, Hur E, Kang S, Kim J, Thapa D, Lee Y, et al. NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1?. Cancer Res. 2011;71:2260-75 pubmed publisher
    Transcription factor NRF2 is an important modifier of cellular responses to oxidative stress...
  70. Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet. 2003;35:238-45 pubmed
    Transcription factor Nrf2 (encoded by Nfe2l2) regulates a battery of detoxifying and antioxidant genes, and Keap1 represses Nrf2 function...
  71. Rada P, Rojo A, Evrard Todeschi N, Innamorato N, Cotte A, Jaworski T, et al. Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/?-TrCP axis. Mol Cell Biol. 2012;32:3486-99 pubmed publisher
    The transcription factor NF-E2-related factor 2 (Nrf2) is a master regulator of a genetic program, termed the phase 2 response, that controls redox homeostasis and participates in multiple aspects of physiology and pathology...
  72. Dhakshinamoorthy S, Jaiswal A. Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. Oncogene. 2001;20:3906-17 pubmed
    Antioxidant response element (ARE) and nuclear transcription factor Nrf2 are known to regulate expression and coordinated induction of NQO1 and other detoxifying enzyme genes in response to antioxidants and xenobiotics...
  73. Zhang D, Lo S, Sun Z, Habib G, Lieberman M, Hannink M. Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. J Biol Chem. 2005;280:30091-9 pubmed
    ..Keap1 targets its substrate, the Nrf2 transcription factor, for ubiquitination and subsequent degradation by the 26 S proteasome...
  74. Kim H, Seo Y. Molecular and genomic approach for understanding the gene-environment interaction between Nrf2 deficiency and carcinogenic nickel-induced DNA damage. Oncol Rep. 2012;28:1959-67 pubmed publisher
    ..Nuclear factor erythroid-2 related factor 2 (Nrf2) is a redox factor that regulates oxidation/reduction status and consequently mediates ..
  75. Thimmulappa R, Fuchs R, Malhotra D, Scollick C, Traore K, Bream J, et al. Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxid Redox Signal. 2007;9:1963-70 pubmed
    Sepsis is characterized by an inappropriate host immune-inflammatory response and sustained oxidative damage. Nrf2, a bZIP oxidant-responsive transcription factor, regulates a battery of cytoprotective genes including antioxidants and ..
  76. Ichikawa T, Li J, Meyer C, Janicki J, Hannink M, Cui T. Dihydro-CDDO-trifluoroethyl amide (dh404), a novel Nrf2 activator, suppresses oxidative stress in cardiomyocytes. PLoS ONE. 2009;4:e8391 pubmed publisher
    Targeting Nrf2 signaling appears to be an attractive approach for the treatment of maladaptive cardiac remodeling and dysfunction; however, pharmacological modulation of the Nrf2 pathway in the cardiovascular system remains to be ..
  77. Mercado N, Thimmulappa R, Thomas C, Fenwick P, Chana K, Donnelly L, et al. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress. Biochem Biophys Res Commun. 2011;406:292-8 pubmed publisher
    Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes...
  78. Nguyen T, Sherratt P, Nioi P, Yang C, Pickett C. Nrf2 controls constitutive and inducible expression of ARE-driven genes through a dynamic pathway involving nucleocytoplasmic shuttling by Keap1. J Biol Chem. 2005;280:32485-92 pubmed
    b>Nrf2 regulates the expression of genes encoding antioxidant proteins involved in cellular redox homeostasis...
  79. Rushworth S, MacEwan D. HO-1 underlies resistance of AML cells to TNF-induced apoptosis. Blood. 2008;111:3793-801 pubmed publisher
    ..region contains antioxidant-response elements that can bind the transcription factor NF-E2-related factor 2 (Nrf2)...
  80. Li W, Yu S, Liu T, Kim J, Blank V, Li H, et al. Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif. Biochim Biophys Acta. 2008;1783:1847-56 pubmed publisher
    b>Nrf2 is the key transcription factor regulating the antioxidant response. When exposed to oxidative stress, Nrf2 translocates to cell nucleus and forms heterodimer with small Maf proteins (sMaf)...
  81. Hayes J, McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 2009;34:176-88 pubmed publisher
    Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant and detoxification genes in response to redox stress...
  82. Shim G, Manandhar S, Shin D, Kim T, Kwak M. Acquisition of doxorubicin resistance in ovarian carcinoma cells accompanies activation of the NRF2 pathway. Free Radic Biol Med. 2009;47:1619-31 pubmed publisher
    It has been firmly established that the transcription factor NRF2 is a critical element in the survival of healthy cells in response to oxidative stress because it up-regulates a wide array of antioxidant genes by binding to the ..
  83. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel J, et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13:76-86 pubmed
    Transcription factor Nrf2 is essential for the antioxidant responsive element (ARE)-mediated induction of phase II detoxifying and oxidative stress enzyme genes...
  84. Hwang Y, Kim H, Han E, Jeong H. Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner. Toxicol Appl Pharmacol. 2008;231:318-27 pubmed publisher
    ..6-OHDA) by a mechanism that involves phosphatidylinositol 3-kinase (PI3K) and ERK kinase/NF-E2-related factor 2 (Nrf2) dependent induction of the stress response protein heme oxygenase-1 (HO-1)...
  85. Kim Y, Ahn J, Liang P, Ip C, Zhang Y, Park Y. Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation: implication to tumor biology. Cancer Res. 2007;67:546-54 pubmed
    ..this study, we cloned the human prx1 promoter and identified nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) as a key transcription factor...
  86. Suzuki M, Betsuyaku T, Ito Y, Nagai K, Nasuhara Y, Kaga K, et al. Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2008;39:673-82 pubmed publisher
    ..are one of the sources of various antioxidant and detoxification enzymes for which NF-E2-related factor 2 (Nrf2) is a key transcriptional factor...
  87. Kim Y, Oh J, Kim M, Kang M, Park S, Han J, et al. Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin. J Pathol. 2010;220:446-51 pubmed publisher
    Nuclear factor erythroid-related factor 2 (NRF2) encodes a transcription factor that induces expression of cytoprotective proteins upon oxidative stress and oncogenic NRF2 mutations have been found in lung and head/neck cancers that ..
  88. Rushworth S, Chen X, Mackman N, Ogborne R, O Connell M. Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C. J Immunol. 2005;175:4408-15 pubmed
    ..genes, contains antioxidant-response elements (AREs) that can bind the transcription factor NF-E2-related factor 2 (Nrf2). At present, the role of Nrf2 in LPS-induced HO-1 expression in monocytic cells has not been investigated...
  89. Seng S, Avraham H, Jiang S, Yang S, Sekine M, Kimelman N, et al. The nuclear matrix protein, NRP/B, enhances Nrf2-mediated oxidative stress responses in breast cancer cells. Cancer Res. 2007;67:8596-604 pubmed
    The transcription factor NF-E2-related factor 2 (Nrf2) translocates into the nucleus and activates phase II genes encoding detoxification enzymes and antioxidant proteins, resulting in the protection of cells from oxidative insults...
  90. Patel R, Maru G. Polymeric black tea polyphenols induce phase II enzymes via Nrf2 in mouse liver and lungs. Free Radic Biol Med. 2008;44:1897-911 pubmed publisher
    ..PBP extract induced transcriptional up-regulation of phase II enzymes in liver and lungs by increasing Nrf2-mediated antioxidant-responsive element (ARE) binding...
  91. Niture S, Jaiswal A. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J Biol Chem. 2012;287:9873-86 pubmed publisher
    Nuclear transcription factor Nrf2 regulates the expression and coordinated induction of a battery of genes encoding cytoprotective and drug transporter proteins in response to chemical and radiation stress...
  92. Li W, Liu H, Zhou J, Cao J, Zhou X, Choi A, et al. Caveolin-1 inhibits expression of antioxidant enzymes through direct interaction with nuclear erythroid 2 p45-related factor-2 (Nrf2). J Biol Chem. 2012;287:20922-30 pubmed publisher
    The Nrf2 (nuclear erythroid 2 p45-related factor-2) signaling pathway is known to play a pivotal role in a variety of oxidative stress-related human disorders...