Gene Symbol: Nfe2l2
Description: nuclear factor, erythroid derived 2, like 2
Alias: Nrf2, nuclear factor erythroid 2-related factor 2, NF-E2-related factor 2, NFE2-related factor 2
Species: mouse
Products:     Nfe2l2

Top Publications

  1. Reisman S, Yeager R, Yamamoto M, Klaassen C. Increased Nrf2 activation in livers from Keap1-knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci. 2009;108:35-47 pubmed publisher
    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor critical for protection against electrophilic and oxidative stress...
  2. Cui W, Li B, Bai Y, Miao X, Chen Q, Sun W, et al. Potential role for Nrf2 activation in the therapeutic effect of MG132 on diabetic nephropathy in OVE26 diabetic mice. Am J Physiol Endocrinol Metab. 2013;304:E87-99 pubmed publisher
    ..Upregulation of the key antioxidative transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), was found to prevent the development of diabetic nephropathy...
  3. Ichimura Y, Waguri S, Sou Y, Kageyama S, Hasegawa J, Ishimura R, et al. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell. 2013;51:618-31 pubmed publisher
    The Keap1-Nrf2 system and autophagy are both involved in the oxidative-stress response, metabolic pathways, and innate immunity, and dysregulation of these processes is associated with pathogenic processes...
  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. 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...
  6. Huebner A, Dai D, Morasso M, Schmidt E, Schafer M, Werner S, et al. Amniotic fluid activates the nrf2/keap1 pathway to repair an epidermal barrier defect in utero. Dev Cell. 2012;23:1238-46 pubmed publisher
    ..5 and E16.5 days postcoitum. In addition, we discovered that the Nrf2/Keap1 pathway detects these compositional changes and directly upregulates the expression of genes involved in the ..
  7. Liu J, Wu K, Lu Y, Ekuase E, Klaassen C. Nrf2 protection against liver injury produced by various hepatotoxicants. Oxid Med Cell Longev. 2013;2013:305861 pubmed publisher
    To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd) and Keap1-hepatocyte knockout (Keap1-HKO) mice were used as a "graded ..
  8. Chartoumpekis D, Ziros P, Zaravinos A, Iskrenova R, Psyrogiannis A, Kyriazopoulou V, et al. Hepatic gene expression profiling in Nrf2 knockout mice after long-term high-fat diet-induced obesity. Oxid Med Cell Longev. 2013;2013:340731 pubmed publisher
    The transcription factor NFE2-related factor 2 (Nrf2) is a central regulator of antioxidant and detoxification gene expression in response to electrophilic or oxidative stress...
  9. Liu R, Chen H, Bai H, Zhang W, Wang X, Qin X, et al. Suppression of nuclear factor erythroid 2-related factor 2 via extracellular signal-regulated kinase contributes to bleomycin-induced oxidative stress and fibrogenesis. Toxicol Lett. 2013;220:15-25 pubmed publisher between oxidative stress and pulmonary fibrogenesis, focusing on nuclear factor erythroid 2-related factor 2 (Nrf2), a core transcription factor in antioxidative regulation systems...

More Information


  1. Kageyama S, Sou Y, Uemura T, Kametaka S, Saito T, Ishimura R, et al. Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway. J Biol Chem. 2014;289:24944-55 pubmed publisher
    ..positive for ubiquitin and p62/Sqstm1, an adaptor protein for both selective autophagy and the anti-oxidative Keap1-Nrf2 pathway...
  2. 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...
  3. Cui Y, Wang Q, Li X, Zhang X. Experimental nonalcoholic fatty liver disease in mice leads to cytochrome p450 2a5 upregulation through nuclear factor erythroid 2-like 2 translocation. Redox Biol. 2013;1:433-40 pubmed publisher
    ..Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor that is post-translationally regulated by oxidative stress and controls the ..
  4. Zhang Y, Wu K, Liu J, Klaassen C. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. Toxicol Appl Pharmacol. 2012;264:305-14 pubmed publisher
    b>Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial...
  5. Ke B, Shen X, Zhang Y, Ji H, Gao F, Yue S, et al. KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver transplants. J Hepatol. 2013;59:1200-7 pubmed publisher
    The Keap1-Nrf2 signaling pathway regulates host cell defense responses against oxidative stress and maintains the cellular redox balance...
  6. Davidson B, Vethanayagam R, Grimm M, Mullan B, Raghavendran K, Blackwell T, et al. NADPH oxidase and Nrf2 regulate gastric aspiration-induced inflammation and acute lung injury. J Immunol. 2013;190:1714-24 pubmed publisher
    ..We hypothesized that NADPH oxidase protects against ALI by limiting neutrophilic inflammation and activating Nrf2, a transcriptional factor that induces antioxidative and cytoprotective pathways...
  7. Uruno A, Furusawa Y, Yagishita Y, Fukutomi T, Muramatsu H, Negishi T, et al. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol. 2013;33:2996-3010 pubmed publisher
    Transcription factor Nrf2 (NF-E2-related factor 2) regulates a broad cytoprotective response to environmental stresses...
  8. Oh C, Kim J, Choi Y, Kim H, Jeong J, Bae K, et al. Dimethylfumarate attenuates renal fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-?/Smad signaling. PLoS ONE. 2012;7:e45870 pubmed publisher
    ..signaling pathway is a possible therapeutic approach for preventing this disease, and reports have suggested that Nrf2 protects against renal fibrosis by inhibiting TGF-? signaling...
  9. Wang C, Cui Y, Li C, Zhang Y, Xu S, Li X, et al. Nrf2 deletion causes "benign" simple steatosis to develop into nonalcoholic steatohepatitis in mice fed a high-fat diet. Lipids Health Dis. 2013;12:165 pubmed publisher
    ..We aimed to test the contribution of nuclear erythroid 2-related factor 2 (Nrf2) on the progression of "benign" SS to NASH in mice fed a high fat diet...
  10. Reddy N, Kleeberger S, Yamamoto M, Kensler T, Scollick C, Biswal S, et al. Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics. 2007;32:74-81 pubmed
    The beta zipper (bZip) transcription factor, nuclear factor erythroid 2, like 2 (Nrf2), acting via an antioxidant/electrophile response element, regulates the expression of several antioxidant enzymes and maintains cellular redox ..
  11. Frohlich D, McCabe M, Arnold R, Day M. The role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis. Oncogene. 2008;27:4353-62 pubmed publisher
    ..Erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) is a basic-region leucine zipper transcription factor that mediates the expression of key protective enzymes ..
  12. Singh A, Rangasamy T, Thimmulappa R, Lee H, Osburn W, Brigelius Flohe R, et al. Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2. Am J Respir Cell Mol Biol. 2006;35:639-50 pubmed
    Disruption of NF-E2-related factor (Nrf2), a redox-sensitive basic leucine zipper transcription factor, causes early-onset and more severe emphysema due to chronic cigarette smoke...
  13. Zhang Y, Crouch D, Yamamoto M, Hayes J. Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum. Biochem J. 2006;399:373-85 pubmed
    Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) and Nrf2 regulate ARE (antioxidant response element)-driven genes. At its N-terminal end, Nrf1 contains 155 additional amino acids that are absent from Nrf2...
  14. Jin W, Wang H, Hu Z, Yan W, Chen G, Yin H. Transcription factor Nrf2 plays a pivotal role in protection against traumatic brain injury-induced acute intestinal mucosal injury in mice. J Surg Res. 2009;157:251-60 pubmed publisher
    ..Nuclear factor erythroid 2-related factor 2 (Nrf2) has a unique role in many physiological stress processes, but its contribution to intestinal mucosal injury after ..
  15. Jiang T, Huang Z, Lin Y, Zhang Z, Fang D, Zhang D. The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy. Diabetes. 2010;59:850-60 pubmed publisher
    ..b>Nrf2 is the primary transcription factor that controls the antioxidant response essential for maintaining cellular redox ..
  16. Osburn W, Karim B, Dolan P, Liu G, Yamamoto M, Huso D, et al. Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2-deficient mice upon dextran sulfate treatment. Int J Cancer. 2007;121:1883-91 pubmed
    ..The transcription factor NF-E2-related factor 2 (Nrf2) controls the expression of numerous antioxidative enzymes that have been shown to attenuate acute inflammation...
  17. Kerns M, DePianto D, Yamamoto M, Coulombe P. Differential modulation of keratin expression by sulforaphane occurs via Nrf2-dependent and -independent pathways in skin epithelia. Mol Biol Cell. 2010;21:4068-75 pubmed publisher
    ..As expected, induction of K16 partly depends on the transcription factor Nrf2, which is activated by SF exposure...
  18. Okada K, Shoda J, Taguchi K, Maher J, Ishizaki K, Inoue Y, et al. Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice. Am J Physiol Gastrointest Liver Physiol. 2008;295:G735-47 pubmed publisher
    ..b>Nrf2, one transcription factor, serves as a cellular stress sensor and is a key regulator for hepatic induction of ..
  19. 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...
  20. Li H, Zhang L, Wang F, Shi Y, Ren Y, Liu Q, et al. Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation. Am J Nephrol. 2011;33:289-97 pubmed publisher
    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a positive regulator of the expression of antioxidant genes...
  21. Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, et al. Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis. J Gastroenterol. 2012;47:924-35 pubmed publisher
    The transcription factor nuclear factor-E2-related factor-2 (Nrf2) is a key regulator for induction of hepatic antioxidative stress systems. We aimed to investigate whether activation of Nrf2 protects against steatohepatitis...
  22. Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, et al. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell. 2012;22:66-79 pubmed publisher
    ..Recent studies revealed that various oncogenic pathways are involved in modulation of metabolism. Nrf2, a key regulator for the maintenance of redox homeostasis, has been shown to contribute to malignant phenotypes of ..
  23. Riley B, Kaiser S, Shaler T, Ng A, Hara T, Hipp M, et al. Ubiquitin accumulation in autophagy-deficient mice is dependent on the Nrf2-mediated stress response pathway: a potential role for protein aggregation in autophagic substrate selection. J Cell Biol. 2010;191:537-52 pubmed publisher Ub conjugates in Atg7(-/-) liver and brain is completely suppressed by simultaneous knockout of either p62 or Nrf2. We exploit a novel assay for selective autophagy in cell culture, which shows that inactivation of Atg5 leads to ..
  24. Liu F, Ichihara S, Valentine W, Itoh K, Yamamoto M, Sheik Mohideen S, et al. Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced hepatotoxicity. Toxicol Sci. 2010;115:596-606 pubmed publisher
    ..the role of oxidative stress in 1-BP-induced hepatotoxicity using nuclear factor erythroid 2-related factor 2 (Nrf2)-null mice...
  25. Jin W, Wang H, Yan W, Xu L, Wang X, Zhao X, et al. Disruption of Nrf2 enhances upregulation of nuclear factor-kappaB activity, proinflammatory cytokines, and intercellular adhesion molecule-1 in the brain after traumatic brain injury. Mediators Inflamm. 2008;2008:725174 pubmed publisher
    ..Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation...
  26. Dinkova Kostova A, Holtzclaw W, Cole R, Itoh K, Wakabayashi N, Katoh Y, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U S A. 2002;99:11908-13 pubmed
    ..Inducers disrupt the cytoplasmic complex between the actin-bound protein Keap1 and the transcription factor Nrf2, thereby releasing Nrf2 to migrate to the nucleus where it activates the antioxidant response element (ARE) of ..
  27. Lee J, Calkins M, Chan K, Kan Y, Johnson J. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem. 2003;278:12029-38 pubmed
    ..In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes and identify Nrf2-dependent genes by ..
  28. Chen W, Sun Z, Wang X, Jiang T, Huang Z, Fang D, et al. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 2009;34:663-73 pubmed publisher
    In response to oxidative stress, Nrf2 and p21(Cip1/WAF1) are both upregulated to protect cells from oxidative damage...
  29. Sussan T, Jun J, Thimmulappa R, Bedja D, Antero M, Gabrielson K, et al. Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice. PLoS ONE. 2008;3:e3791 pubmed publisher
    Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes ..
  30. Kraft A, Resch J, Johnson D, Johnson J. Activation of the Nrf2-ARE pathway in muscle and spinal cord during ALS-like pathology in mice expressing mutant SOD1. Exp Neurol. 2007;207:107-17 pubmed
    ..Subsequently, Nrf2-ARE activation appears to progress in a retrograde fashion along the motor pathway...
  31. Cho M, Kim W, Ki S, Hwang J, Choi S, Lee C, et al. Role of Galpha12 and Galpha13 as novel switches for the activity of Nrf2, a key antioxidative transcription factor. Mol Cell Biol. 2007;27:6195-208 pubmed
    Galpha12 and Galpha13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress...
  32. Kraft A, Johnson D, Johnson J. Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult. J Neurosci. 2004;24:1101-12 pubmed
    Binding of the transcription factor nuclear factor E2-related factor 2 (Nrf2) to the antioxidant response element (ARE) in neural cells results in the induction of a battery of genes that can coordinate a protective response against a ..
  33. Martin F, van Deursen J, Shivdasani R, Jackson C, Troutman A, Ney P. Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and nrf-2. Blood. 1998;91:3459-66 pubmed
    ..Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is not the result of compensation by Nrf-2. ..
  34. Shih A, Imbeault S, Barakauskas V, Erb H, Jiang L, Li P, et al. Induction of the Nrf2-driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem. 2005;280:22925-36 pubmed
    NF-E2 related factor (Nrf2) controls a pleiotropic cellular defense, where multiple antioxidant/detoxification pathways are up-regulated in unison...
  35. He C, Gong P, Hu B, Stewart D, Choi M, Choi A, et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 2001;276:20858-65 pubmed
    b>Nrf2 regulates expression of genes encoding enzymes with antioxidant (e.g. heme oxygenase-1 (HO-1)) or xenobiotic detoxification (e.g...
  36. Khor T, Huang M, Kwon K, Chan J, Reddy B, Kong A. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res. 2006;66:11580-4 pubmed
    ..Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been known to be a transcriptional factor which plays a crucial role in cytoprotection against inflammation, ..
  37. 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...
  38. Jain A, Lamark T, Sjøttem E, Larsen K, Awuh J, Øvervatn A, et al. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem. 2010;285:22576-91 pubmed publisher
    ..Induction of the p62 gene by oxidative stress is mediated by NF-E2-related factor 2 (NRF2) and, at the same time, p62 protein contributes to the activation of NRF2, but hitherto the mechanisms involved ..
  39. Maher J, Dieter M, Aleksunes L, Slitt A, Guo G, Tanaka Y, et al. Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology. 2007;46:1597-610 pubmed
    ..that is, the disruption of hepatic GSH synthesis) or the administration of nuclear factor-E2-related factor-2 (Nrf2) activators (oltipraz and butylated hydroxyanisole) can induce hepatic Mrp transporters and whether that induction ..
  40. McMahon M, Itoh K, Yamamoto M, Hayes J. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem. 2003;278:21592-600 pubmed
    Keap1 is a negative regulator of Nrf2, a bZIP transcription factor that mediates adaptation to oxidative stress...
  41. Zheng H, Whitman S, Wu W, Wondrak G, Wong P, Fang D, et al. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes. 2011;60:3055-66 pubmed publisher
    To determine whether dietary compounds targeting NFE2-related factor 2 (Nrf2) activation can be used to attenuate renal damage and preserve renal function during the course of streptozotocin (STZ)-induced diabetic nephropathy...
  42. Jin W, Zhu L, Guan Q, Chen G, Wang Q, Yin H, et al. Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory response after traumatic brain injury. Ann Clin Lab Sci. 2008;38:221-7 pubmed
    ..Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that plays a crucial role in cytoprotection against inflammation...
  43. Lee J, Chan K, Kan Y, Johnson J. Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia. Proc Natl Acad Sci U S A. 2004;101:9751-6 pubmed
    A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and ..
  44. Shin S, Wakabayashi N, Misra V, Biswal S, Lee G, Agoston E, et al. NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis. Mol Cell Biol. 2007;27:7188-97 pubmed
    The NF-E2 p45-related factor 2 (NRF2) and the aryl hydrocarbon receptor (AHR) are transcription factors controlling pathways modulating xenobiotic metabolism. AHR has recently been shown to affect Nrf2 expression...
  45. 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...
  46. Yan W, Wang H, Hu Z, Wang Q, Yin H. Activation of Nrf2-ARE pathway in brain after traumatic brain injury. Neurosci Lett. 2008;431:150-4 pubmed
    ..Therefore, a target, which can interrupt multi-mechanisms underlying TBI, is desirable. Nrf2-ARE pathway has been proved to be the key regulator in reducing oxidative stress, inflammatory damage and ..
  47. Reisman S, Csanaky I, Aleksunes L, Klaassen C. Altered disposition of acetaminophen in Nrf2-null and Keap1-knockdown mice. Toxicol Sci. 2009;109:31-40 pubmed publisher
    ..Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that mitigates electrophilic stress from AA by inducing genes, such as NAD(P)H:quinone ..
  48. Sussan T, Rangasamy T, Blake D, Malhotra D, El Haddad H, Bedja D, et al. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc Natl Acad Sci U S A. 2009;106:250-5 pubmed publisher
    ..Nuclear erythroid 2 p45 related factor-2 (Nrf2) is a redox-sensitive transcription factor that up-regulates a battery of antioxidative genes and cytoprotective ..
  49. Nakamura B, Lawson G, Chan J, Banuelos J, Cortés M, Hoang Y, et al. Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med. 2010;49:1368-79 pubmed publisher
    ..The transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) regulates basal and inducible transcription of genes encoding enzymes important for protection against ROS...
  50. auf dem Keller U, Huber M, Beyer T, Kümin A, Siemes C, Braun S, et al. Nrf transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing. Mol Cell Biol. 2006;26:3773-84 pubmed
    The Nrf2 transcription factor is a key player in the cellular stress response through its regulation of cytoprotective genes...
  51. Mimoto T, Miyazaki K, Morimoto N, Kurata T, Satoh K, Ikeda Y, et al. Impaired antioxydative Keap1/Nrf2 system and the downstream stress protein responses in the motor neuron of ALS model mice. Brain Res. 2012;1446:109-18 pubmed publisher
    The Kelch-like ECH-associated protein 1 (Keap1)/Nuclear erythroid 2-related factor 2 (Nrf2) system is the major cellular defense mechanism under oxidative stress, but the role in motor neuron degeneration under amyotrophic lateral ..
  52. Wang X, Hayes J, Henderson C, Wolf C. Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha. Proc Natl Acad Sci U S A. 2007;104:19589-94 pubmed
    Isothiocyanates and phenolic antioxidants can prevent cancer through activation of Nrf2 (NF-E2 p45-related factor 2), a transcription factor that controls expression of cytoprotective genes through the antioxidant response element (ARE) ..
  53. Li Y, Takizawa H, Azuma A, Kohyama T, Yamauchi Y, Takahashi S, et al. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clin Immunol. 2008;128:366-73 pubmed publisher the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks...
  54. Leiser S, Miller R. Nrf2 signaling, a mechanism for cellular stress resistance in long-lived mice. Mol Cell Biol. 2010;30:871-84 pubmed publisher
    Transcriptional regulation of the antioxidant response element (ARE) by Nrf2 is important for the cellular adaptive response to toxic insults...
  55. Johnson D, Amirahmadi S, Ward C, Fabry Z, Johnson J. The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. Toxicol Sci. 2010;114:237-46 pubmed publisher
    ..Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that regulates genetic expression of many protective antioxidant ..
  56. He X, Chen M, Lin G, Ma Q. Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 x Keap1 x Cul3 complex and recruiting Nrf2 x Maf to the antioxidant response element enhancer. J Biol Chem. 2006;281:23620-31 pubmed
    ..and biochemical evidence revealed that induction required cap 'n' collar basic leucine zipper transcription factor Nrf2 and the antioxidant response element (ARE) of Nqo1...
  57. Kraft A, Lee J, Johnson D, Kan Y, Johnson J. Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element. J Neurochem. 2006;98:1852-65 pubmed
    The transcription factor, nuclear factor E2 (erythroid-derived 2)-related factor 2 (Nrf2), is essential for the induction of a battery of phase II detoxification genes through the antioxidant response element (ARE) that lies in their ..
  58. Apopa P, He X, Ma Q. Phosphorylation of Nrf2 in the transcription activation domain by casein kinase 2 (CK2) is critical for the nuclear translocation and transcription activation function of Nrf2 in IMR-32 neuroblastoma cells. J Biochem Mol Toxicol. 2008;22:63-76 pubmed publisher
    The antioxidant-activated transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the induction of cytoprotective genes against chemical toxicity and oxidative injuries...
  59. Calvert J, Jha S, Gundewar S, Elrod J, Ramachandran A, Pattillo C, et al. Hydrogen sulfide mediates cardioprotection through Nrf2 signaling. Circ Res. 2009;105:365-74 pubmed publisher
    ..During the early preconditioning period, H(2)S increased the nuclear localization of Nrf2, a transcription factor that regulates the gene expression of a number of antioxidants and increased the ..
  60. Iida K, Itoh K, Kumagai Y, Oyasu R, Hattori K, Kawai K, et al. Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res. 2004;64:6424-31 pubmed
    ..Transcription factor Nrf2 is an essential regulator of the inducible expression of detoxifying enzyme genes by chemopreventive agents...
  61. 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...
  62. Osburn W, Yates M, Dolan P, Chen S, Liby K, Sporn M, et al. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol Sci. 2008;104:218-27 pubmed publisher
    ..The transcription factor NF-E2-related factor 2 (Nrf2) regulates the expression of a battery of antioxidative enzymes and Nrf2 signaling can be activated by small-..
  63. Slitt A, Cherrington N, Dieter M, Aleksunes L, Scheffer G, Huang W, et al. trans-Stilbene oxide induces expression of genes involved in metabolism and transport in mouse liver via CAR and Nrf2 transcription factors. Mol Pharmacol. 2006;69:1554-63 pubmed
    ..TSO increased nuclear staining of the transcription factor Nrf2 in liver, and activated an antioxidant/electrophile response element luciferase reporter construct that was ..
  64. Leonard M, Kieran N, Howell K, Burne M, Varadarajan R, Dhakshinamoorthy S, et al. Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury. FASEB J. 2006;20:2624-6 pubmed
    ..The transcription factor NF-E2-related factor-2 (Nrf2), a master regulator of this antioxidant response, is also elevated in IRI...
  65. Wang H, Khor T, Saw C, Lin W, Wu T, Huang Y, et al. Role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages by polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid. Mol Pharm. 2010;7:2185-93 pubmed publisher
    This study is to investigate the role of Nrf2 in suppressing LPS-mediated inflammation in ex vivo macrophages by polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)...
  66. Hou Y, Xue P, Bai Y, Liu D, Woods C, Yarborough K, et al. Nuclear factor erythroid-derived factor 2-related factor 2 regulates transcription of CCAAT/enhancer-binding protein ? during adipogenesis. Free Radic Biol Med. 2012;52:462-72 pubmed publisher
    Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) is a cap-n-collar basic leucine zipper transcription factor that is involved in the cellular adaptive response to oxidative stress...
  67. Taguchi K, Maher J, Suzuki T, Kawatani Y, Motohashi H, Yamamoto M. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol Cell Biol. 2010;30:3016-26 pubmed publisher
    Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes...
  68. Cho H, Imani F, Miller DeGraff L, Walters D, Melendi G, Yamamoto M, et al. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med. 2009;179:138-50 pubmed publisher
    ..The transcription factor Nrf2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene ..
  69. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236:313-22 pubmed
    ..The expression profiles of a number of transcription factors suggest that an Nrf2/small Maf heterodimer is the most likely candidate to fulfill this role in vivo...
  70. Nguyen T, Nioi P, Pickett C. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009;284:13291-5 pubmed publisher
    A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in ..
  71. Ramos Gomez M, Kwak M, Dolan P, Itoh K, Yamamoto M, Talalay P, et al. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A. 2001;98:3410-5 pubmed
    ..The transcription factor Nrf2, which binds to the ARE, appears to be essential for the induction of prototypical phase 2 enzymes such as ..
  72. Reddy N, Kleeberger S, Bream J, Fallon P, Kensler T, Yamamoto M, et al. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene. 2008;27:5821-32 pubmed publisher
    Genetic disruption of Nrf2 greatly enhances susceptibility to prooxidant- and carcinogen-induced experimental models of various human disorders; but the mechanisms by which this transcription factor confers protection are unclear...
  73. Copple I, Lister A, Obeng A, Kitteringham N, Jenkins R, Layfield R, et al. Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. J Biol Chem. 2010;285:16782-8 pubmed publisher
    b>Nrf2 regulates the expression of numerous cytoprotective genes in mammalian cells. The activity of Nrf2 is regulated by the Cul3 adaptor Keap1, yet little is known regarding mechanisms of regulation of Keap1 itself...
  74. Vollrath V, Wielandt A, Iruretagoyena M, Chianale J. Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem J. 2006;395:599-609 pubmed
    The Nrf2 (nuclear factor-erythroid 2 p45-related factor 2) transcription factor regulates gene expression of the GCLC (glutamate-cysteine ligase catalytic subunit), which is a key enzyme in glutathione synthesis, and GSTs (glutathione S-..
  75. Zhao J, Moore A, Redell J, Dash P. Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury. J Neurosci. 2007;27:10240-8 pubmed
    ..Activation of the transcription factor NF-E2-related factor-2 (Nrf2) by sulforaphane, a naturally occurring compound present in high levels in cruciferous vegetables, significantly ..
  76. Kang M, Kobayashi A, Wakabayashi N, Kim S, Yamamoto M. Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. Proc Natl Acad Sci U S A. 2004;101:2046-51 pubmed
    Transcription factor Nrf2 regulates basal and inducible expression of phase 2 proteins that protect animal cells against the toxic effects of electrophiles and oxidants...
  77. Schafer M, Farwanah H, Willrodt A, Huebner A, Sandhoff K, ROOP D, et al. Nrf2 links epidermal barrier function with antioxidant defense. EMBO Mol Med. 2012;4:364-79 pubmed publisher
    ..Here, we show that these essential functions are linked through the Nrf2 transcription factor...
  78. Jyrkkänen H, Kansanen E, Inkala M, Kivelä A, Hurttila H, Heinonen S, et al. Nrf2 regulates antioxidant gene expression evoked by oxidized phospholipids in endothelial cells and murine arteries in vivo. Circ Res. 2008;103:e1-9 pubmed publisher
    ..that oxPAPC could evoke a general cytoprotective response via activation of antioxidative transcription factor Nrf2. Here, we show that oxPAPC increases nuclear accumulation of Nrf2...
  79. Harvey C, Thimmulappa R, Singh A, Blake D, Ling G, Wakabayashi N, et al. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med. 2009;46:443-53 pubmed publisher
    Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is the primary transcription factor protecting cells from oxidative stress by regulating cytoprotective genes, including the antioxidant glutathione (GSH) pathway...
  80. Zhu H, Itoh K, Yamamoto M, Zweier J, Li Y. Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury. FEBS Lett. 2005;579:3029-36 pubmed
    ..Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 ..
  81. Jakel R, Townsend J, Kraft A, Johnson J. Nrf2-mediated protection against 6-hydroxydopamine. Brain Res. 2007;1144:192-201 pubmed
    ..Under oxidative stress conditions, the transcription factor NF-E2-related factor (Nrf2) binds to the antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes...
  82. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213-23 pubmed publisher
    ..Here we report the identification of a novel regulatory mechanism by p62 of the transcription factor Nrf2, whose target genes include antioxidant proteins and detoxification enzymes...
  83. Kanki K, Umemura T, Kitamura Y, Ishii Y, Kuroiwa Y, Kodama Y, et al. A possible role of nrf2 in prevention of renal oxidative damage by ferric nitrilotriacetate. Toxicol Pathol. 2008;36:353-61 pubmed publisher
    To ascertain the possible roles of nuclear erythroid 2 p45-related factor 2 (Nrf2), a key transcription factor of phase 2 drug-metabolizing enzymes, in renal cellular defense against oxidative stress, wild-type and Nrf2-knockout -/- mice ..
  84. Kwak M, Itoh K, Yamamoto M, Kensler T. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol. 2002;22:2883-92 pubmed
    ..The transcription factor Nrf2, which binds to the antioxidant response element (ARE) found in the upstream regulatory region of many phase 2 ..
  85. Harada N, Kanayama M, Maruyama A, Yoshida A, Tazumi K, Hosoya T, et al. Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages. Arch Biochem Biophys. 2011;508:101-9 pubmed publisher
    ..In this study, we demonstrated genetically that a redox-sensitive transcription factor, Nrf2, regulates Fpn1 mRNA expression in macrophages...
  86. Tanaka Y, Aleksunes L, Yeager R, Gyamfi M, Esterly N, Guo G, et al. NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther. 2008;325:655-64 pubmed publisher
    NF-E2-related factor 2 (Nrf2) is a transcription factor that is activated by oxidative stress and electrophiles that regulates the expression of numerous detoxifying and antioxidant genes...