Gene Symbol: Nfe2l1
Description: nuclear factor, erythroid derived 2,-like 1
Alias: AA408798, AW212678, LCR-F1, Lcrf1, NRF1, TCF-11, TCF11, endoplasmic reticulum membrane sensor NFE2L1, nuclear factor erythroid 2-related factor 1, NF-E2-related factor 1, NFE2-related factor 1, locus control region-factor 1
Species: mouse
Products:     Nfe2l1

Top Publications

  1. Shivdasani R, Orkin S. Erythropoiesis and globin gene expression in mice lacking the transcription factor NF-E2. Proc Natl Acad Sci U S A. 1995;92:8690-4 pubmed
    ..Thus, regulation of globin gene transcription through NF-E2 binding sites in vivo is more complex than has been previously appreciated. ..
  2. Kobayashi A, Ito E, Toki T, Kogame K, Takahashi S, Igarashi K, et al. Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3. J Biol Chem. 1999;274:6443-52 pubmed
    ..Recently, two p45-related factors Nrf1 and Nrf2 were isolated, and they are now collectively grouped as the Cap'n' collar (CNC) family...
  3. 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
    b>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...
  4. Narayanan K, Ramachandran A, Peterson M, Hao J, Kolstø A, Friedman A, et al. The CCAAT enhancer-binding protein (C/EBP)beta and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation. J Biol Chem. 2004;279:45423-32 pubmed
    ..expression of the DSPP gene, we have identified a novel interaction between two bZIP transcription factors, Nrf1 and the CCAAT enhancer-binding protein (C/EBP)beta...
  5. Xu Z, Chen L, Leung L, Yen T, Lee C, Chan J. Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc Natl Acad Sci U S A. 2005;102:4120-5 pubmed
    Knockout studies have shown that the transcription factor Nrf1 is essential for embryonic development...
  6. Lee C, Lee C, Hu T, Nguyen J, Zhang J, Martin M, et al. Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration. Proc Natl Acad Sci U S A. 2011;108:8408-13 pubmed publisher
    ..Nuclear factor E2-related factor 1 (Nrf1) transcription factor has been shown to regulate expression of antioxidant and cytoprotective genes...
  7. Xing W, Singgih A, Kapoor A, Alarcon C, Baylink D, Mohan S. Nuclear factor-E2-related factor-1 mediates ascorbic acid induction of osterix expression via interaction with antioxidant-responsive element in bone cells. J Biol Chem. 2007;282:22052-61 pubmed
    ..mechanisms by which AA regulates osteoblast differentiation, we examined the effect of AA on osterix expression via Nrf1 (NF-E2-related factor-1) binding to antioxidant-responsive element (ARE) in bone marrow stromal (BMS) cells...
  8. Radhakrishnan S, Lee C, Young P, Beskow A, Chan J, Deshaies R. Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol Cell. 2010;38:17-28 pubmed publisher
    ..Here, we report that nuclear factor erythroid-derived 2-related factor 1 (Nrf1), a transcription factor of the cap "n" collar basic leucine zipper family, but not the related Nrf2, is ..
  9. Wang W, Chan J. Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function. J Biol Chem. 2006;281:19676-87 pubmed
    ..response elements involves members of the CNC (Cap 'n' Collar) family of basic leucine zipper proteins including Nrf1 and Nrf2. Nrf2 activity is regulated by Keap1-mediated compartmentalization in the cell...

More Information


  1. Tsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, et al. Dual regulation of the transcriptional activity of Nrf1 by ?-TrCP- and Hrd1-dependent degradation mechanisms. Mol Cell Biol. 2011;31:4500-12 pubmed publisher
    A growing body of evidence suggests that Nrf1 is an inducible transcription factor that maintains cellular homeostasis...
  2. Chan J, Kwong M, Lu R, Chang J, Wang B, Yen T, et al. Targeted disruption of the ubiquitous CNC-bZIP transcription factor, Nrf-1, results in anemia and embryonic lethality in mice. EMBO J. 1998;17:1779-87 pubmed
    ..To determine the function of Nrf-1, targeted disruption of the Nrf-1 gene was carried out. Homozygous Nrf-1 mutant mice are anemic due to a non-cell autonomous defect in definitive erythropoiesis and die in utero. ..
  3. Ohtsuji M, Katsuoka F, Kobayashi A, Aburatani H, Hayes J, Yamamoto M. Nrf1 and Nrf2 play distinct roles in activation of antioxidant response element-dependent genes. J Biol Chem. 2008;283:33554-62 pubmed publisher
    b>Nrf1 is a member of the vertebrate Cap'n'Collar (CNC) transcription factor family that commonly contains a unique basic-leucine zipper domain...
  4. Zhang Y, Lucocq J, Yamamoto M, Hayes J. The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem J. 2007;408:161-72 pubmed
    b>Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is negatively controlled by its NTD (N-terminal domain) that lies between amino acids 1 and 124...
  5. Hirotsu Y, Higashi C, Fukutomi T, Katsuoka F, Tsujita T, Yagishita Y, et al. Transcription factor NF-E2-related factor 1 impairs glucose metabolism in mice. Genes Cells. 2014;19:650-65 pubmed publisher
    b>Nrf1 (NF-E2-related factor 1) is a basic region leucine zipper-type transcription factor belonging to the CNC (cap-'n'-collar) family. Major pathophysiological contribution of Nrf1 remains unclear...
  6. Kwong E, Kim K, Penalosa P, Chan J. Characterization of Nrf1b, a novel isoform of the nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes. PLoS ONE. 2012;7:e48404 pubmed publisher
    Nuclear factor E2-related factor 1 (Nrf1) is a basic leucine zipper transcription factor that plays an important role in the activation of cytoprotective genes through the antioxidant response elements...
  7. Hirotsu Y, Hataya N, Katsuoka F, Yamamoto M. NF-E2-related factor 1 (Nrf1) serves as a novel regulator of hepatic lipid metabolism through regulation of the Lipin1 and PGC-1? genes. Mol Cell Biol. 2012;32:2760-70 pubmed publisher
    ..NF-E2-related factor 1 (Nrf1) is a member of the cap'n'collar (CNC) transcription factor family...
  8. Song M, Mattie M, Lee C, Freedman J. The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Exp Cell Res. 2014;322:39-50 pubmed publisher
    Recent evidences indicated Nrf2 is more potent than Nrf1 in the activation of antioxidant genes. However, the roles of Nrf proteins in the regulation of copper-responsive transcription have not been well addressed...
  9. Chen L, Kwong M, Lu R, Ginzinger D, Lee C, Leung L, et al. Nrf1 is critical for redox balance and survival of liver cells during development. Mol Cell Biol. 2003;23:4673-86 pubmed
    The Nrf1 transcription factor belongs to the CNC subfamily of basic leucine zipper proteins. Knockout of Nrf1 is lethal in mouse embryos, but nothing is known about the cell types that absolutely require its function during development...
  10. Hamazaki J, Hirayama S, Murata S. Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and Cellular Homeostasis. PLoS Genet. 2015;11:e1005401 pubmed publisher
    ..Our results indicate that Rpn13 mostly plays a redundant role with Rpn10 in recognition of ubiquitinated proteins and maintaining homeostasis in Mus musculus. ..
  11. Prieschl E, Novotny V, Csonga R, Jaksche D, Elbe Bürger A, Thumb W, et al. A novel splice variant of the transcription factor Nrf1 interacts with the TNFalpha promoter and stimulates transcription. Nucleic Acids Res. 1998;26:2291-7 pubmed
    ..Here, we show that in the context of the FcgammaRIII, the gamma chain activates the transcription factor Nrf1 or a closely related protein that specifically interacts with the extended kappa3 site in the TNFalpha promoter...
  12. Sotzny F, Schormann E, Kühlewindt I, Koch A, Brehm A, Goldbach Mansky R, et al. TCF11/Nrf1-Mediated Induction of Proteasome Expression Prevents Cytotoxicity by Rotenone. Antioxid Redox Signal. 2016;25:870-885 pubmed
    ..We have previously shown that the transcription factor TCF11/Nrf1 induces antioxidant response element-mediated upregulation of UPS components in response to proteotoxic ..
  13. Ho D, Chan J. Induction of Herpud1 expression by ER stress is regulated by Nrf1. FEBS Lett. 2015;589:615-20 pubmed publisher
    ..The Nrf1 transcription factor is important in cellular stress pathways...
  14. Tsuchiya Y, Taniguchi H, Ito Y, Morita T, Karim M, Ohtake N, et al. The casein kinase 2-nrf1 axis controls the clearance of ubiquitinated proteins by regulating proteasome gene expression. Mol Cell Biol. 2013;33:3461-72 pubmed publisher
    ..Here we show that the protein kinase casein kinase 2 (CK2) regulates the transcriptional activity of Nrf1 to control the expression of the proteasome genes and thus the clearance of ubiquitinated proteins...
  15. Zhang Y, Xiang Y. Molecular and cellular basis for the unique functioning of Nrf1, an indispensable transcription factor for maintaining cell homoeostasis and organ integrity. Biochem J. 2016;473:961-1000 pubmed publisher
    ..antioxidant-response elements) and/or EpREs (electrophile-response elements) allow for differential recruitment of Nrf1 [NF-E2 (nuclear factor-erythroid 2)-related factor 1], Nrf2 and Nrf3, together with each of their heterodimeric ..
  16. Leung L, Kwong M, Hou S, Lee C, Chan J. Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. J Biol Chem. 2003;278:48021-9 pubmed
    b>Nrf1 and Nrf2 are members of the CNC family of bZIP transcription factors that exhibit structural similarities, and they are co-expressed in a wide range of tissues during development...
  17. Novotny V, Prieschl E, Csonga R, Fabjani G, Baumruker T. Nrf1 in a complex with fosB, c-jun, junD and ATF2 forms the AP1 component at the TNF alpha promoter in stimulated mast cells. Nucleic Acids Res. 1998;26:5480-5 pubmed
    ..Here we show that the three CNC-bZIP members NF-E2, Nrf1 and Nrf2 are constitutively expressed in the murine mast cell line CPII and that they form transcription factor ..
  18. Meixner A, Karreth F, Kenner L, Penninger J, Wagner E. Jun and JunD-dependent functions in cell proliferation and stress response. Cell Death Differ. 2010;17:1409-19 pubmed publisher
    ..In Jun(-/-) fetal livers, increased hydrogen peroxide levels are detected and expression of Nrf1 and Nrf2 (nuclear erythroid 2-related transcription factors) is downregulated...
  19. Molofsky A, Glasgow S, Chaboub L, Tsai H, Murnen A, Kelley K, et al. Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia. 2013;61:1518-32 pubmed publisher
    ..5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control...
  20. Widenmaier S, Snyder N, Nguyen T, Arduini A, Lee G, Arruda A, et al. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis. Cell. 2017;171:1094-1109.e15 pubmed publisher
    ..Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process...
  21. Zhang Y, Nicholatos J, Dreier J, Ricoult S, Widenmaier S, Hotamisligil G, et al. Coordinated regulation of protein synthesis and degradation by mTORC1. Nature. 2014;513:440-3 pubmed publisher
    ..on induction of the transcription factor nuclear factor erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1)...
  22. Furuya N, Ikeda S, Sato S, Soma S, Ezaki J, Oliva Trejo J, et al. PARK2/Parkin-mediated mitochondrial clearance contributes to proteasome activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation. Autophagy. 2014;10:631-41 pubmed publisher
    ..Denervation induced proteasomal activation via NFE2L1 nuclear translocation in control mice, whereas it had little effect in autophagy-deficient and Park2-deficient ..
  23. Chui D, Tang W, Orkin S. cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor. Biochem Biophys Res Commun. 1995;209:40-6 pubmed
    ..The murine Nrf 2 gene is expressed not only in erythroid cells, but also in the 3T3 murine fibroblast cell line. ..
  24. McKie J, Scambler P. The Nfe2l1 gene maps to distal mouse chromosome 11. Mamm Genome. 1996;7:89 pubmed
  25. Oh D, Rigas D, Cho A, Chan J. Deficiency in the nuclear-related factor erythroid 2 transcription factor (Nrf1) leads to genetic instability. FEBS J. 2012;279:4121-30 pubmed publisher
    Nuclear factor erythroid-derived 2-related factor 1 (Nrf1) regulates cellular stress response genes, and has also been suggested to play a role in other cellular processes...
  26. Cullinan S, Zhang D, Hannink M, Arvisais E, Kaufman R, Diehl J. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol. 2003;23:7198-209 pubmed
    ..Our data demonstrate that Nrf2 is a critical effector of PERK-mediated cell survival. ..
  27. Tsujita T, Peirce V, Baird L, Matsuyama Y, Takaku M, Walsh S, et al. Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes. Mol Cell Biol. 2014;34:3800-16 pubmed publisher
    Liver-specific Nrf1 (NF-E2-p45-related factor 1) knockout mice develop nonalcoholic steatohepatitis...
  28. Murphy P, Kolstø A. Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development. Mech Dev. 2000;97:141-8 pubmed
    b>TCF11 (also known as Nrf1 and LCR-F1) is a basic-region leucine-zipper (b-ZIP) transcription factor that is essential during embryonic development...
  29. Zhang Y, Qiu L, Li S, Xiang Y, Chen J, Ren Y. The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression. PLoS ONE. 2014;9:e109159 pubmed publisher
    The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor...
  30. Tong K, Katoh Y, Kusunoki H, Itoh K, Tanaka T, Yamamoto M. Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model. Mol Cell Biol. 2006;26:2887-900 pubmed
    ..Based on these observations, we propose that Keap1 recruits Nrf2 by the ETGE motif and that the DLG motif of the Neh2 domain locks its lysine-rich central alpha-helix in a correct position to benefit ubiquitin signaling. ..
  31. Dhar S, Liang H, Wong Riley M. Transcriptional coupling of synaptic transmission and energy metabolism: role of nuclear respiratory factor 1 in co-regulating neuronal nitric oxide synthase and cytochrome c oxidase genes in neurons. Biochim Biophys Acta. 2009;1793:1604-13 pubmed publisher
    ..These findings are consistent with our hypothesis that synaptic neuronal transmission and energy metabolism are tightly coupled at the molecular level. ..
  32. Kim J, Xing W, Wergedal J, Chan J, Mohan S. Targeted disruption of nuclear factor erythroid-derived 2-like 1 in osteoblasts reduces bone size and bone formation in mice. Physiol Genomics. 2010;40:100-10 pubmed publisher
    Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of ..
  33. Kobayashi A, Tsukide T, Miyasaka T, Morita T, Mizoroki T, Saito Y, et al. Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction. Genes Cells. 2011;16:692-703 pubmed publisher
    ..In this study, we examined the contribution of Nrf1, one of the CNC proteins, to neuronal homeostasis in vivo...
  34. McKie J, Johnstone K, Mattei M, Scambler P. Cloning and mapping of murine Nfe2l1. Genomics. 1995;25:716-9 pubmed
    The murine homologue of the human NFE2L1 basic leucine-zipper gene was isolated from an early embryo library. The deduced amino acid sequence shows 97% identity between the two proteins...
  35. Koch A, Steffen J, Krüger E. TCF11 at the crossroads of oxidative stress and the ubiquitin proteasome system. Cell Cycle. 2011;10:1200-7 pubmed
    ..proteasome system, thereby focussing on Nrf2 as well as on the recently identified transcription factor (TF) TCF11. In response to proteasome inhibition TCF11 plays a central role in upregulating the proteasome system via an ERAD-..
  36. Cui Q, Fu J, Hu Y, Li Y, Yang B, Li L, et al. Deficiency of long isoforms of Nfe2l1 sensitizes MIN6 pancreatic ? cells to arsenite-induced cytotoxicity. Toxicol Appl Pharmacol. 2017;329:67-74 pubmed publisher
    ..Like nuclear factor erythroid 2 like 2 (NFE2L2), NFE2L1 also belongs to the cap 'n' collar (CNC) basic-region leucine zipper (bZIP) transcription factor family, and ..
  37. Lee C, Ho D, Chan J. Nuclear factor-erythroid 2-related factor 1 regulates expression of proteasome genes in hepatocytes and protects against endoplasmic reticulum stress and steatosis in mice. FEBS J. 2013;280:3609-20 pubmed publisher
    The ubiquitin-proteasome system is important in maintaining protein homeostasis. NFE2-related factor 1 (Nrf1), a transcription factor in the cap 'n' collar basic-leucine zipper family, regulates expression of cytoprotective genes...
  38. Farmer S, Sun C, Winnier G, Hogan B, Townes T. The bZIP transcription factor LCR-F1 is essential for mesoderm formation in mouse development. Genes Dev. 1997;11:786-98 pubmed
    ..To assess the role of LCR-F1 in mammalian development, the mouse Lcrf1 gene was deleted in embryonic stem (ES) cells, and mice derived from these cells were mated to produce Lcrf1 null ..
  39. Chen J, Liu X, Lü F, Liu X, Ru Y, Ren Y, et al. Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status. FEBS Lett. 2015;589:2347-58 pubmed publisher
    ..The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression...