Affinage

NFE2

Transcription factor NF-E2 45 kDa subunit · UniProt Q16621

Length
373 aa
Mass
41.5 kDa
Annotated
2026-04-29
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFE2 (p45 NF-E2) is a hematopoietic-specific CNC-family basic-leucine zipper transcription factor essential for terminal megakaryocyte maturation, proplatelet formation, and erythroid differentiation. It forms obligate heterodimers with small Maf proteins (MafF, MafG, MafK) to bind NF-E2/AP-1-like recognition elements in globin locus control regions and in megakaryocyte-specific gene promoters including thromboxane synthase, β1 tubulin, and Rab27b, with DNA-binding activity augmented by CBP-mediated acetylation of MafG (PMID:8469283, PMID:8107826, PMID:11154691, PMID:9312024, PMID:10942379, PMID:12907454). NFE2 activity is regulated by competing partners (Bach1, Fos–Maf homodimers) for small Maf binding, by upstream transcriptional activation through AML1/RUNX1, and by an autoregulatory loop involving the histone demethylase JMJD1C that modulates H3K9 methylation at the NFE2 promoter (PMID:8887638, PMID:7891713, PMID:20339092, PMID:29519804). Overexpression or acquired truncating mutations of NFE2 cause myeloproliferative neoplasms with thrombocytosis and predisposition to leukemic transformation (PMID:22231305, PMID:23589569, PMID:30755419).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Identification of NFE2 as a hematopoietic bZIP factor that heterodimerizes with a small subunit to bind AP-1-like sites in globin LCRs established the molecular identity of the NF-E2 complex and its role in erythroid gene regulation.

    Evidence cDNA cloning, protein purification, DNA-binding assays, and in vitro transcription with NF-E2-site mutagenesis

    PMID:8265578 PMID:8423810 PMID:8469283

    Open questions at the time
    • Identity of the small subunit not yet resolved as Maf family
    • In vivo target gene specificity unknown
  2. 1994 High

    Demonstrating that small Maf proteins (MafF/G/K) are the obligate heterodimeric partners of p45 resolved the composition of functional NF-E2 and revealed that Maf homodimers act as repressors, establishing a competitive dimerization paradigm.

    Evidence In vitro dimerization and transcription assays in erythroid cells

    PMID:8107826

    Open questions at the time
    • Relative contributions of individual small Mafs in different lineages unknown
    • In vivo stoichiometry unresolved
  3. 1996 High

    Discovery that Bach1, Fos, and other bZIP factors compete with p45 for small Maf binding at NF-E2 sites established a partner-exchange regulatory network controlling erythroid and stress-response gene expression.

    Evidence Yeast two-hybrid, in vitro DNA binding, transfection assays, and later heme-induced ChIP showing Bach1 displacement

    PMID:14747657 PMID:7891713 PMID:8887638

    Open questions at the time
    • Relative affinities and kinetics of partner exchange in vivo not quantified
    • Signals governing Bach1–NF-E2 switching beyond heme not fully defined
  4. 1999 High

    Analysis of NF-E2-knockout mice revealed that p45 is essential for platelet biogenesis and erythrocyte maturation, with thrombocytopenia resulting from a late block in megakaryocyte differentiation and failure of integrin αIIbβ3 activation.

    Evidence NF-E2-null mice with bone marrow transplantation, fibrinogen binding, and complementation assays

    PMID:10556187 PMID:10613901

    Open questions at the time
    • Full repertoire of NF-E2-dependent megakaryocyte genes not catalogued
    • Mechanism of integrin activation defect unclear
  5. 2000 High

    Identification of β1 tubulin and confirmation of NF-E2 occupancy at the β-globin LCR HS2 in living cells defined direct transcriptional targets linking NF-E2 to cytoskeletal proplatelet formation and globin regulation.

    Evidence ChIP in erythroleukemia and fetal liver cells; mRNA subtraction between NF-E2-null and WT megakaryocytes with rescue

    PMID:10891470 PMID:10942379

    Open questions at the time
    • Whether NF-E2 is required for LCR-mediated chromatin looping not resolved
  6. 2001 High

    CBP-mediated acetylation of MafG in its basic region augments NF-E2 DNA binding and transactivation, establishing post-translational modification of the heterodimeric partner as a regulatory mechanism.

    Evidence In vitro acetyltransferase assays, co-immunoprecipitation, mutagenesis, transfection reporter assays

    PMID:11154691

    Open questions at the time
    • In vivo dynamics of MafG acetylation during differentiation unknown
    • Other acetyltransferases not tested
  7. 2003 High

    NF-E2 directly activates Rab27b in megakaryocytes, linking NF-E2 to granule transport and proplatelet formation through a vesicle-trafficking effector.

    Evidence ChIP at Rab27b promoter, immunofluorescence localization, dominant-negative Rab27 inhibition in primary megakaryocytes

    PMID:12907454

    Open questions at the time
    • Full set of granule-trafficking genes controlled by NF-E2 not defined
  8. 2007 High

    Chromosome conformation capture in NF-E2-null erythroid cells demonstrated that NF-E2 is dispensable for β-globin active chromatin hub formation, refining NF-E2's role to transcriptional activation rather than long-range chromatin looping.

    Evidence 3C assays in NF-E2-knockout mouse erythroid cells

    PMID:17428799

    Open questions at the time
    • Precise step at which NF-E2 acts after chromatin hub assembly not defined
  9. 2010 High

    Identifying NFE2 as a direct transcriptional target of AML1/RUNX1 placed NFE2 downstream of a key megakaryocyte master regulator and explained elevated NFE2 in polycythemia vera.

    Evidence ChIP at NFE2 promoter, RNAi knockdown of AML1/CBFβ, promoter-reporter assays in patient granulocytes

    PMID:20339092

    Open questions at the time
    • Whether RUNX1-driven NFE2 upregulation is sufficient for MPN initiation not tested
  10. 2012 High

    Transgenic overexpression of NF-E2 caused myeloproliferative neoplasm features with histone H3 hypoacetylation, reversible by HDAC inhibitors, establishing NFE2 gain-of-function as oncogenic in myeloid neoplasia.

    Evidence NF-E2 transgenic mouse model, bone marrow transplantation, histone modification analysis, HDAC inhibitor rescue

    PMID:22231305

    Open questions at the time
    • Direct chromatin targets mediating the MPN phenotype not identified
  11. 2013 High

    Acquired truncating NFE2 mutations in MPN patients produce gain-of-function proteins that enhance wild-type NF-E2 activity and confer clonal dominance, providing a genetic mechanism for disease progression.

    Evidence Patient mutation sequencing, murine expression model, clonal competition assays

    PMID:23589569

    Open questions at the time
    • Structural basis for gain-of-function by truncated proteins unknown
  12. 2016 High

    Genome-wide co-occupancy mapping showed NF-E2 collaborates with FLI1 and RUNX1 at late-acting megakaryocyte enhancers marked by high H3K4me2, defining the combinatorial code for terminal platelet gene activation.

    Evidence ChIP-seq for NF-E2, FLI1, RUNX1, and histone marks in primary megakaryocytes

    PMID:27457419

    Open questions at the time
    • Causal hierarchy among NF-E2, FLI1, and RUNX1 at co-occupied enhancers not resolved
  13. 2018 High

    Discovery of a JMJD1C–NFE2 autoregulatory loop, where NFE2 induces JMJD1C which demethylates H3K9 at the NFE2 promoter to sustain NFE2 expression, revealed an epigenetic feedforward mechanism exploited by JAK2V617F-driven MPN.

    Evidence ChIP at JMJD1C and NFE2 promoters, histone modification analysis, pharmacological perturbation in JAK2V617F cells and patient samples

    PMID:29519804

    Open questions at the time
    • Whether disrupting the JMJD1C–NFE2 loop is therapeutically sufficient in MPN is untested
  14. 2019 High

    Longitudinal modeling showed NFE2 mutations predispose to AML transformation with acquisition of secondary lesions including Trp53 loss and trisomy 8 equivalent, establishing NFE2 as a driver of leukemic evolution.

    Evidence Mouse modeling of NFE2 mutations with cytogenetic and mutation analysis of transformed tumors, validated in human AML

    PMID:30755419

    Open questions at the time
    • Whether NFE2 mutations directly cause genomic instability or simply provide a selective advantage is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for how truncated NFE2 mutant proteins enhance wild-type function, the full catalog of direct NF-E2 target genes in megakaryocytes versus erythroid cells, and whether targeting the JMJD1C–NFE2 autoregulatory loop can prevent leukemic transformation remain open questions.
  • No crystal structure of NF-E2–Maf heterodimer available
  • Genome-wide NF-E2 target gene sets in erythroid cells not comprehensively validated
  • Therapeutic strategies targeting NFE2 overexpression in MPN not clinically tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-109582 Hemostasis 3 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3
Partners
BACH1CREBBPFLI1JMJD1CMAFFMAFGMAFKRUNX1
Complex memberships
NF-E2 (p45-small Maf heterodimer)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 NFE2 (p45 NF-E2) is a hematopoietic-specific basic-leucine zipper protein that dimerizes with a ubiquitous partner (p18) to form the functional NF-E2 heterodimer, which binds AP-1-like recognition sites in globin locus control regions. cDNA cloning, protein purification, DNA binding assays Nature High 8469283
1993 The ubiquitous p18 subunit of NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene, and forms the obligate heterodimeric partner with p45 NF-E2 for DNA binding. Protein purification, cDNA cloning, sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 8265578
1994 Small Maf proteins (MafF, MafG, MafK) directly control the DNA-binding properties of p45 NF-E2 through heterodimeric association; Maf homodimers act as negative regulators while p45-Maf heterodimers support active transcription, establishing that small Maf proteins are the second constituent chain of NF-E2. In vitro dimerization assays, transcription assays in erythroid cells, transfection experiments Nature High 8107826
1993 NF-E2 binding to AP-1/NF-E2 sites in the beta-globin locus control region enhancer is required for enhancer-dependent transcription of epsilon-globin, while GATA-1 binding at the promoter mediates the enhancer-promoter interaction. In vitro transcription, site-directed mutagenesis of NF-E2 sites Molecular and cellular biology High 8423810
1995 Small Maf proteins can also heterodimerize with Fos, and Fos-small Maf heterodimers cannot activate NF-E2 site-dependent transcription, suggesting competitive regulation of erythroid gene expression among Fos, NF-E2 p45, and small Maf proteins. In vitro DNA binding, co-immunoprecipitation, transfection assays Molecular and cellular biology High 7891713
1996 Bach1 and Bach2, novel BTB-bZip transcription factors, heterodimerize with MafK and bind NF-E2 sites in vitro; they function as transcriptional repressors in fibroblasts but Bach1 acts as an activator in erythroid cells, competing with p45 NF-E2 for MafK binding. Yeast two-hybrid screen, in vitro DNA binding, transfection assays Molecular and cellular biology High 8887638
1997 p45 NF-E2 directly regulates the thromboxane synthase (TXS) gene in megakaryocytes through functional NF-E2 binding sites in its promoter and an intronic chromatin-dependent enhancer; p45-null megakaryocytes lack TXS mRNA. In vivo chromatin immunoprecipitation/immunoselection, promoter/enhancer reporter assays, p45-null mouse analysis The EMBO journal High 9312024
1998 In primary megakaryocytes, p45 NF-E2 is the only large subunit that dimerizes with small Maf proteins; MafG and/or MafF predominate in megakaryocytes (unlike MafK in erythroid cells), and the NF-E2 complex preferentially binds an asymmetric AP-1-related motif. Nuclear extract preparation, EMSA, biochemical characterization of primary megakaryocytes The Journal of biological chemistry High 9516460
1998 NF-E2 activity (both DNA binding and transactivation) is upregulated during erythroid differentiation in erythroleukemia cells via serine/threonine phosphorylation through the Ras-Raf-MAP kinase cascade; MafK homodimers suppress transcription by direct inhibition in addition to DNA site competition. Kinase inhibitor experiments, domain analysis, transient transfection assays, DMSO-induced differentiation The Journal of biological chemistry Medium 9478996
1999 NF-E2-deficient megakaryocytes fail to activate alphaIIbbeta3 integrin in response to agonists despite normal surface expression, establishing that NF-E2 controls signaling pathways required for integrin activation that mature late in megakaryocyte development. Primary megakaryocytes from NF-E2 knockout mice, fibrinogen binding assays, Sindbis virus-mediated gene expression The Journal of cell biology High 10613901
1999 Mice lacking p45 NF-E2 have profound thrombocytopenia due to late arrest in megakaryocyte differentiation with reduced proliferation potential, and also develop erythroid abnormalities including anisocytosis, hypochromia, and small red blood cell fragments, establishing NF-E2 as required for both megakaryocyte and erythrocyte maturation. NF-E2 knockout mice, splenectomy, bone marrow transplantation, hematopoietic cell transfer Blood High 10556187
2000 NF-E2 binds directly and specifically to the tandem Maf recognition elements of hypersensitive site 2 (HS2) of the beta-globin locus control region in living erythroleukemia cells and fetal liver, dependent on p45 and intact MAREs. Chromatin immunoprecipitation assay in intact cells Blood High 10891470
2000 NF-E2 transcriptionally regulates beta1 tubulin expression in megakaryocytes; NF-E2-deficient megakaryocytes lack beta1 tubulin mRNA/protein, and restoring NF-E2 rescues beta1 tubulin expression, linking NF-E2 to microtubule-based proplatelet formation. mRNA subtraction between NF-E2-null and wild-type megakaryocytes, NF-E2 rescue experiments in primary cells and cell lines Blood High 10942379
2001 CBP acetyltransferase physically interacts with both p45 NF-E2 and MafG subunits; CBP acetylates MafG predominantly in the basic region, and MafG acetylation augments NF-E2 DNA binding activity; mutations at major acetylation sites markedly reduce DNA binding and transcriptional activation. Co-immunoprecipitation in vitro and in vivo, acetyltransferase assays, mutagenesis, transfection reporter assays The Journal of biological chemistry High 11154691
2001 Human ITCH protein interacts with p45 NF-E2 (identified by yeast two-hybrid) and functions as a transcriptional corepressor of NF-E2 in transfection experiments. Yeast two-hybrid, transfection corepressor assays Genomics Medium 11318614
2003 NF-E2 transcriptionally regulates Rab27b expression in megakaryocytes; ChIP demonstrates NF-E2 recruitment to the Rab27B promoter; Rab27b localizes to alpha and dense granules, and inhibition of Rab27 function causes severe defects in proplatelet formation. Chromatin immunoprecipitation, subcellular localization (immunofluorescence), dominant-negative inhibition in primary megakaryocytes Blood High 12907454
2004 Heme induces displacement of Bach1 from MafK-occupied ho-1 enhancers and subsequent Nrf2 binding, accompanied by de novo histone H3 hyperacetylation and hypermethylation in the transcribed region, establishing heme as a signaling molecule that drives partner exchange in the small Maf transcription factor network. Chromatin immunoprecipitation assays in NIH 3T3 cells, histone modification analysis Proceedings of the National Academy of Sciences of the United States of America High 14747657
2007 In differentiating erythroid cells, formation of the beta-globin active chromatin hub (ACH) requires GATA-1 and EKLF but not p45 NF-E2; NF-E2 is dispensable for ACH formation as shown in p45 NF-E2 knockout mice. Chromosome conformation capture (3C), knock-out mouse analysis, erythroid differentiation model The Journal of biological chemistry High 17428799
2009 In megakaryocytes, p45 NF-E2 dominates over Nrf2 at shared cytoprotective gene targets, acting as a less efficacious activator to maintain moderate expression, thereby promoting ROS accumulation that in turn enhances platelet gene expression and megakaryocytic maturation. Comprehensive gene expression profiling in wild-type and p45-null megakaryocytes, competition assays between p45 and Nrf2 Blood High 19901266
2010 AML1/RUNX1 directly binds the NF-E2 promoter in vivo and transcriptionally activates NF-E2 expression; AML1 binding is increased in granulocytes from polycythemia vera patients; RNAi knockdown of AML1 or its partner CBF-beta decreases NF-E2 expression, identifying NF-E2 as a novel AML1 target gene. Chromatin immunoprecipitation, RNAi knockdown, promoter characterization, NF-E2 promoter-reporter assays Blood High 20339092
2012 Overexpression of NF-E2 in hematopoietic cells causes myeloproliferative neoplasm features including thrombocytosis and leukocytosis; NF-E2 transgenic mice show hypoacetylation of histone H3, and HDAC inhibitor treatment restores H3 acetylation, decreases NF-E2 expression, and normalizes platelet numbers. NF-E2 transgenic mouse model, bone marrow transplantation, histone modification analysis, HDAC inhibitor treatment The Journal of experimental medicine High 22231305
2013 Acquired truncating insertion/deletion mutations in NFE2 found in MPN patients produce truncated NF-E2 proteins that enhance wild-type NF-E2 function; expression in mice causes erythrocytosis and thrombocytosis, and mutant cells acquire clonal dominance over wild-type NF-E2 cells. Mutation sequencing in MPN patients, murine model of mutant NFE2 expression, clonal analysis The Journal of experimental medicine High 23589569
2016 NF-E2 co-occupies late-acting cis-regulatory enhancers with FLI1 and RUNX1 in terminal megakaryocyte maturation; co-occupancy by NF-E2 with either RUNX1 or FLI1 gives the highest H3K4me2 histone signals and correlates with genes activated late in megakaryocyte differentiation responsible for platelet assembly and release. ChIP-seq for NF-E2, FLI1, RUNX1, and histone marks; genome-wide chromatin dynamics analysis in primary megakaryocytes Scientific reports High 27457419
2017 NFE2 directly induces miR-423-5p expression to repress the FAM3A-ATP-Akt pathway in hepatocytes, promoting gluconeogenesis, lipid deposition, and hyperglycemia; hepatic NFE2 overexpression phenocopies this pathway activation in normal mice. miRNA target validation, reporter assays, NFE2 overexpression in mouse liver, siRNA knockdown Diabetes Medium 28411267
2018 Histone demethylase JMJD1C is a novel NFE2 target gene; JMJD1C in turn binds the NFE2 promoter, decreasing H3K9me2 levels and HP1α binding to autoregulate NFE2 expression; separately, JAK2V617F-driven H3Y41 phosphorylation also inhibits HP1α binding to activate NFE2 expression. ChIP at JMJD1C and NFE2 promoters, histone modification analysis, decitabine treatment in JAK2V617F cell lines Blood High 29519804
2019 NFE2 mutations in AML patients and in MPN patients predispose to leukemic transformation; NF-E2 mutant mice develop myelosarcomas and AML acquiring secondary mutations including trisomy 8 equivalent, chromosome 5q deletions, and Trp53 mutations. Longitudinal mouse modeling of NFE2 mutations, cytogenetic and mutation analysis of transformed tumors Blood High 30755419
1995 Two alternatively spliced isoforms of NF-E2 (aNF-E2 and fNF-E2) differ in their 5' untranslated regions and are expressed in different ratios during development (fNF-E2 predominates in fetal liver; aNF-E2 in adult bone marrow), though both produce the same protein. cDNA library screening, RT-PCR, developmental expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 7724591
2003 Mice deficient in NF-E2 (or GATA-1) show 200–300% increases in bone volume and formation; osteoblast proliferation increases up to 6-fold when cultured with NF-E2-deficient megakaryocytes by a mechanism requiring cell-to-cell contact, revealing a megakaryocyte-osteoblast interaction dependent on the excess immature megakaryocytes produced in NF-E2 null mice. Histomorphometry, microCT, in vitro co-culture of osteoblasts with NF-E2-null megakaryocytes Journal of bone and mineral research Medium 15005853
2014 Rho kinase (ROCK) inhibition drives megakaryocyte polyploidization and proplatelet formation, coinciding with downregulation of NFE2 expression in mature megakaryocytes, suggesting a model where ROCK inhibition drives late megakaryocyte maturation through NFE2 downregulation. ROCK inhibitor treatment of cord blood-derived megakaryocytes, proplatelet formation assay, gene expression analysis British journal of haematology Low 24383889

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Nature 598 8469283
1996 Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site. Molecular and cellular biology 567 8887638
1996 NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proceedings of the National Academy of Sciences of the United States of America 565 8943040
1994 Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature 417 8107826
2005 Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells. Biochemical and biophysical research communications 344 15882976
2004 Heme regulates the dynamic exchange of Bach1 and NF-E2-related factors in the Maf transcription factor network. Proceedings of the National Academy of Sciences of the United States of America 311 14747657
1993 Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proceedings of the National Academy of Sciences of the United States of America 304 8248256
2003 NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. The Journal of biological chemistry 268 12842875
2003 Atypical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress. American journal of physiology. Cell physiology 267 12700136
1993 The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proceedings of the National Academy of Sciences of the United States of America 250 8265578
2008 Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. American journal of respiratory cell and molecular biology 244 18566336
2002 Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Molecular pharmacology 244 12391262
2008 NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. The Journal of pharmacology and experimental therapeutics 218 18281592
1995 Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor. Molecular and cellular biology 215 7891713
2008 Activation of NF-E2-related factor-2 reverses biochemical dysfunction of endothelial cells induced by hyperglycemia linked to vascular disease. Diabetes 195 18633117
2017 Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2). Cellular and molecular gastroenterology and hepatology 173 29552625
2012 The transcription factor NF-E2-related factor 2 (Nrf2): a protooncogene? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 159 23109674
2005 Transcriptional regulation of thioredoxin reductase 1 expression by cadmium in vascular endothelial cells: role of NF-E2-related factor-2. Journal of cellular physiology 159 15521073
2012 Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis. American journal of respiratory and critical care medicine 158 22312014
2011 Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway. Journal of agricultural and food chemistry 152 21355597
2011 Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. American journal of physiology. Heart and circulatory physiology 147 21217061
2010 NF-E2-related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection. Arteriosclerosis, thrombosis, and vascular biology 145 20947826
2010 Regulation of NF-E2-related factor 2 signaling for cancer chemoprevention: antioxidant coupled with antiinflammatory. Antioxidants & redox signaling 144 20486765
2006 Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in endothelial cells: role of reactive oxygen/nitrogen species. Free radical biology & medicine 141 17189831
2005 Ultraviolet A irradiation induces NF-E2-related factor 2 activation in dermal fibroblasts: protective role in UVA-induced apoptosis. The Journal of investigative dermatology 140 15816842
2000 Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2. Blood 133 10942379
2011 Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. Free radical biology & medicine 121 22155056
2006 Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells. Free radical biology & medicine 121 16962933
1993 Isolation of cDNA encoding the human NF-E2 protein. Proceedings of the National Academy of Sciences of the United States of America 117 8248255
2017 The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NF-E2. Antioxidants & redox signaling 115 28006954
2003 Megakaryocyte-osteoblast interaction revealed in mice deficient in transcription factors GATA-1 and NF-E2. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 112 15005853
1997 Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif. Oncogene 102 9150357
2012 NF-E2-related factor 1 (Nrf1) serves as a novel regulator of hepatic lipid metabolism through regulation of the Lipin1 and PGC-1β genes. Molecular and cellular biology 91 22586274
2009 NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation. Blood 91 19901266
2000 Direct interaction of NF-E2 with hypersensitive site 2 of the beta-globin locus control region in living cells. Blood 90 10891470
2012 Dimethylfumarate attenuates renal fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. PloS one 89 23056222
2011 Nrf2b, novel zebrafish paralog of oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2). The Journal of biological chemistry 89 22174413
1999 Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2. Blood 85 10556187
2012 Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal. Cell & bioscience 81 23190551
2013 Attenuation of β-amyloid-induced oxidative cell death by sulforaphane via activation of NF-E2-related factor 2. Oxidative medicine and cellular longevity 78 23864927
2001 Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-mediated acetylation. The Journal of biological chemistry 78 11154691
2017 NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes 77 28411267
2003 A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 77 12907454
1997 p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. The EMBO journal 76 9312024
2009 Active NF-E2-related factor (Nrf2) contributes to keep endothelial NO synthase (eNOS) in the coupled state: role of reactive oxygen species (ROS), eNOS, and heme oxygenase (HO-1) levels. The Journal of biological chemistry 74 19797052
1998 The NF-E2 transcription factor. The international journal of biochemistry & cell biology 74 9675875
2018 Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. Free radical biology & medicine 72 30342186
2010 Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression. American journal of physiology. Gastrointestinal and liver physiology 72 20395535
2012 A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2. The Journal of experimental medicine 71 22231305
1999 Primary megakaryocytes reveal a role for transcription factor NF-E2 in integrin alpha IIb beta 3 signaling. The Journal of cell biology 70 10613901
2013 Paeoniflorin protects human EA.hy926 endothelial cells against gamma-radiation induced oxidative injury by activating the NF-E2-related factor 2/heme oxygenase-1 pathway. Toxicology letters 67 23403272
2013 MPN patients harbor recurrent truncating mutations in transcription factor NF-E2. The Journal of experimental medicine 67 23589569
2017 Role of NF-E2 related factor 2 (Nrf2) on chemotherapy resistance in acute myeloid leukemia (AML) and the effect of pharmacological inhibition of Nrf2. PloS one 66 28505160
2010 CR6-interacting factor 1 (CRIF1) regulates NF-E2-related factor 2 (NRF2) protein stability by proteasome-mediated degradation. The Journal of biological chemistry 66 20427290
1998 Regulation of NF-E2 activity in erythroleukemia cell differentiation. The Journal of biological chemistry 66 9478996
2015 The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation. Redox biology 65 26773873
2012 Loss of transcription factor nuclear factor-erythroid 2 (NF-E2) p45-related factor-2 (Nrf2) leads to dysregulation of immune functions, redox homeostasis, and intracellular signaling in dendritic cells. The Journal of biological chemistry 63 22311972
2007 Beta-globin active chromatin Hub formation in differentiating erythroid cells and in p45 NF-E2 knock-out mice. The Journal of biological chemistry 60 17428799
2012 Laminar flow activation of ERK5 protein in vascular endothelium leads to atheroprotective effect via NF-E2-related factor 2 (Nrf2) activation. The Journal of biological chemistry 59 23043106
2006 Hepatic ischemia-reperfusion induces renal heme oxygenase-1 via NF-E2-related factor 2 in rats and mice. Molecular pharmacology 59 17151289
1995 cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor. Biochemical and biophysical research communications 59 7726861
1993 Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2. Molecular and cellular biology 58 8423810
2007 Triphlorethol-A induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor. FEBS letters 56 17467702
1998 Characterization of the hematopoietic transcription factor NF-E2 in primary murine megakaryocytes. The Journal of biological chemistry 56 9516460
1997 Regulation of the serum concentration of thrombopoietin in thrombocytopenic NF-E2 knockout mice. Blood 56 9292514
2006 Low and high dose UVB regulation of transcription factor NF-E2-related factor 2. Cancer research 53 16951152
2017 Targeting the NF-E2-Related Factor 2 Pathway: a Novel Strategy for Traumatic Brain Injury. Molecular neurobiology 51 28224478
1995 Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. Human genetics 51 7868116
2011 Epigallocatechin-gallate stimulates NF-E2-related factor and heme oxygenase-1 via caveolin-1 displacement. The Journal of nutritional biochemistry 50 21447442
2008 The susceptibility to vitiligo is associated with NF-E2-related factor2 (Nrf2) gene polymorphisms: a study on Chinese Han population. Experimental dermatology 50 18537816
1999 Identification of NRF2, a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases. Cell death and differentiation 50 10510468
2015 Dipeptidyl peptidase-4 inhibition by gemigliptin prevents abnormal vascular remodeling via NF-E2-related factor 2 activation. Vascular pharmacology 49 26187356
2010 AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2. Blood 48 20339092
2007 NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells. Chemical research in toxicology 47 17676812
2015 Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells. Cellular and molecular life sciences : CMLS 45 25721735
2013 Seven in absentia homolog 2 (Siah2) protein is a regulator of NF-E2-related factor 2 (Nrf2). The Journal of biological chemistry 45 23645672
2013 Developmental expression of the Nfe2-related factor (Nrf) transcription factor family in the zebrafish, Danio rerio. PloS one 45 24298298
2015 Tanshinone IIA protects dopaminergic neurons against 6-hydroxydopamine-induced neurotoxicity through miR-153/NF-E2-related factor 2/antioxidant response element signaling pathway. Neuroscience 43 26116522
2018 NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland. Thyroid : official journal of the American Thyroid Association 42 29742982
2022 The Effects of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (Nrf2) Activation in Preclinical Models of Peripheral Neuropathic Pain. Antioxidants (Basel, Switzerland) 41 35204312
2022 Characterisation of the Circulating Transcriptomic Landscape in Inflammatory Bowel Disease Provides Evidence for Dysregulation of Multiple Transcription Factors Including NFE2, SPI1, CEBPB, and IRF2. Journal of Crohn's & colitis 41 35212366
2013 Role of migratory inhibition factor in age-related susceptibility to radiation lung injury via NF-E2-related factor-2 and antioxidant regulation. American journal of respiratory cell and molecular biology 41 23526214
2017 NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway. Digestive diseases and sciences 40 28815354
2013 Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model. Oncology reports 40 23673813
2014 Transcription factor NF-E2-related factor 1 impairs glucose metabolism in mice. Genes to cells : devoted to molecular & cellular mechanisms 38 25041126
2018 Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms. Blood 37 29519804
2013 Trichostatin A inhibits transforming growth factor-β-induced reactive oxygen species accumulation and myofibroblast differentiation via enhanced NF-E2-related factor 2-antioxidant response element signaling. Molecular pharmacology 35 23284002
2009 The expression of NF-E2-related factor 2 in the rat brain after traumatic brain injury. The Journal of trauma 35 19430250
2014 Rho kinase inhibition drives megakaryocyte polyploidization and proplatelet formation through MYC and NFE2 downregulation. British journal of haematology 33 24383889
2012 The HDAC inhibitor Givinostat modulates the hematopoietic transcription factors NFE2 and C-MYB in JAK2(V617F) myeloproliferative neoplasm cells. Experimental hematology 33 22579713
2019 Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations. Blood 32 30755419
1999 Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells. Oncogene 31 10498903
2018 Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: Implications for obesity-associated colon carcinogenesis. Biochemical pharmacology 30 29427626
2016 NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes. Scientific reports 29 27457419
2012 Elevated hepatic iron activates NF-E2-related factor 2-regulated pathway in a dietary iron overload mouse model. Toxicological sciences : an official journal of the Society of Toxicology 28 22649188
2007 NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo. Experimental hematology 27 17923245
1997 NF-E2p18/mafK is required in DMSO-induced differentiation of Friend erythroleukemia cells by enhancing NF-E2 activity. Leukemia 26 9009092
2016 Accumulation of phosphorylated p62 is associated with NF-E2-related factor 2 activation in hepatocellular carcinoma. Journal of hepato-biliary-pancreatic sciences 25 27246794
2001 Human ITCH is a coregulator of the hematopoietic transcription factor NF-E2. Genomics 25 11318614
1995 Isolation of a differentially regulated splicing isoform of human NF-E2. Proceedings of the National Academy of Sciences of the United States of America 25 7724591