Affinage

NFE2

Transcription factor NF-E2 45 kDa subunit · UniProt Q16621

Length
373 aa
Mass
41.5 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFE2 (p45 NF-E2) is a hematopoietic-specific basic-leucine zipper transcription factor that drives erythroid and megakaryocytic gene programs by binding AP-1-like Maf-recognition elements as an obligate heterodimer with ubiquitous small Maf proteins (MafF, MafG, MafK) (PMID:8469283, PMID:8107826). The p45–small Maf ratio sets the transcriptional output: p45-Maf heterodimers activate transcription while small Maf homodimers act as negative regulators, and Fos can compete for small Maf partners to repress NF-E2 targets (PMID:8107826, PMID:7891713, PMID:9478996). Distinct small Mafs predominate in different lineages—MafG/MafF in megakaryocytes, MafK in erythroid cells—providing combinatorial control over a shared DNA-binding specificity (PMID:9516460). In erythroid cells NF-E2 is recruited to the beta-globin locus control region MAREs (HS2, HS4) during differentiation, where it is required for hypersensitive-site formation and drives a large increase in beta-globin transcription, in part by promoting RNA Pol II CTD Ser5 phosphorylation together with USF (PMID:7828582, PMID:10891470, PMID:11517325, PMID:20236933). In megakaryocytes NF-E2 is the essential driver of terminal maturation and platelet biogenesis, directly activating a battery of late-acting targets including thromboxane synthase, beta1-tubulin, Rab27b, LIMS1, P-selectin (Selp), and Myl9, and its loss produces profound thrombocytopenia from late differentiation arrest (PMID:9312024, PMID:10556187, PMID:10942379, PMID:12907454, PMID:17047147, PMID:23648484). NF-E2 co-occupies late megakaryocyte enhancers with FLI1 and RUNX1, with RUNX1 in turn directly activating the NFE2 promoter, and it competes with Nrf2 at cytoprotective genes to promote ROS-driven maturation (PMID:19901266, PMID:20339092, PMID:27457419). Its activity is tuned by post-translational and chromatin mechanisms—sumoylation at K368 enhancing DNA binding and transactivation, CBP-mediated acetylation of MafG augmenting DNA binding, PKA- and MAP-kinase-dependent phosphorylation, a WWP1 PPXY-1 interaction required for transactivation, ITCH corepression, and a JMJD1C/JAK2 H3-modification autoregulatory loop (PMID:9753456, PMID:7721832, PMID:11154691, PMID:16287851, PMID:11318614, PMID:29519804). A V173A missense mutation impairs NF-E2 in mk mice causing defective globin production and iron metabolism, and acquired truncating NFE2 mutations confer clonal proliferative advantage in myeloproliferative neoplasms (PMID:8469289, PMID:23589569). Beyond hematopoiesis, hepatic NFE2 induces miR-423-5p to repress the FAM3A-ATP-Akt pathway and promote gluconeogenesis (PMID:28411267).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 High

    Establishing the molecular identity of NF-E2 answered what protein bound erythroid LCR AP-1-like sites, defining it as a hematopoietic bZIP factor requiring a dimerization partner.

    Evidence cDNA cloning and biochemical DNA-binding/dimerization analysis of p45 NF-E2

    PMID:8469283

    Open questions at the time
    • Identity of the obligate partner subunit not yet defined
    • In vivo target genes not characterized
  2. 1993 High

    A V173A mutation in mk mice linked p45 NF-E2 activity directly to globin production and iron metabolism in vivo.

    Evidence DNA sequencing of mk alleles with expression analysis in erythroid tissue and duodenum

    PMID:8469289

    Open questions at the time
    • Mechanism connecting NF-E2 to iron absorption not resolved
    • Molecular consequence of V173A on DNA binding not detailed
  3. 1994 High

    Identifying small Maf proteins as the partner subunits explained how NF-E2 output is positively or negatively tuned by the p45:Maf ratio.

    Evidence small Maf cloning, in vitro dimerization, and in vivo reporter transcription assays

    PMID:8107826 PMID:9009092 PMID:9150357

    Open questions at the time
    • Lineage-specific Maf usage not yet established
    • Structural basis of heterodimer DNA specificity not defined
  4. 1995 High

    Mutational dissection in chromatin context showed NF-E2 sites are functionally required for LCR hypersensitive-site formation, moving beyond in vitro binding to chromatin function.

    Evidence Site-directed mutagenesis of HS4 element in stably transfected MEL cells with nuclease sensitivity assays; antisense loss-of-function in progenitors

    PMID:7738198 PMID:7828582 PMID:7891713

    Open questions at the time
    • Whether binding causes or follows chromatin opening unresolved
    • Role outside HS4/HS2 not addressed
  5. 1999 High

    Knockout and transplantation defined the cell-intrinsic in vivo requirement for NF-E2 in megakaryocyte maturation and platelet production.

    Evidence p45 NF-E2 knockout mice with bone marrow transplantation and splenectomy

    PMID:10556187

    Open questions at the time
    • Downstream effector genes not yet enumerated
    • Molecular basis of late differentiation arrest unknown
  6. 2003 High

    Identification of direct megakaryocyte targets (TXS, beta1-tubulin, Rab27b) explained how NF-E2 loss arrests platelet biogenesis, while rescue showed no single target suffices.

    Evidence ChIP, promoter/enhancer assays, expression in NF-E2-null cells, and functional rescue in primary megakaryocytes

    PMID:10942379 PMID:12907454 PMID:9312024 PMID:9516460

    Open questions at the time
    • Complete target set required for proplatelet formation not defined
    • Coordination of multiple targets during maturation unclear
  7. 2001 High

    Temporal ChIP and post-translational studies revealed how NF-E2 recruitment is gated and amplified, distinguishing pre-differentiation Maf-only occupancy from active heterodimer recruitment.

    Evidence ChIP across LCR loci before/after differentiation; CBP acetylation assays; WWP1 PPXY binding; PKA/MAPK phosphorylation; ITCH corepression

    PMID:10891470 PMID:11154691 PMID:11318614 PMID:11517325 PMID:7721832 PMID:9478996 PMID:9753456

    Open questions at the time
    • Integration of multiple regulatory inputs not modeled
    • ITCH interaction not confirmed by reciprocal Co-IP
  8. 2005 High

    Sumoylation at K368 was shown to be functionally required for NF-E2 LCR binding and beta-globin activation, defining a specific activating modification.

    Evidence In vitro sumoylation, K368R mutagenesis, ChIP, rescue in p45-null cells, and PML body colocalization

    PMID:16287851

    Open questions at the time
    • Responsible SUMO ligase not identified
    • Dynamics of sumoylation during differentiation unresolved
  9. 2009 High

    Genetic and genome-wide analysis showed NF-E2 competes with Nrf2 at cytoprotective genes to promote ROS-driven megakaryocyte maturation, reconciling earlier independence of the two factors.

    Evidence Genome-wide expression profiling, p45/Nrf2 compound mutants, and ROS measurement

    PMID:19901266 PMID:9538217

    Open questions at the time
    • Mechanism by which moderate target expression drives maturation incompletely defined
    • Direct ROS effector genes not fully mapped
  10. 2013 High

    Genome-wide ChIP-seq plus regulatory and disease studies placed NF-E2 within a megakaryocyte enhancer network and linked acquired NFE2 mutations to myeloproliferative clonal advantage.

    Evidence ChIP-seq with FLI1/RUNX1, hypomorphic and overexpression mouse models, RUNX1 promoter ChIP, MPN patient sequencing, and JMJD1C/JAK2 autoregulatory analysis

    PMID:17423245 PMID:20339092 PMID:23589569 PMID:23648484 PMID:27457419 PMID:29519804

    Open questions at the time
    • How truncated NF-E2 enhances wild-type function mechanistically unclear
    • Relative contribution of each enhancer partner to specific targets not dissected
  11. 2017 Medium

    A hepatic role was uncovered in which NFE2 induces miR-423-5p to repress FAM3A-ATP-Akt signaling and promote gluconeogenesis, extending function beyond hematopoiesis.

    Evidence ChIP/reporter for miR-423 promoter binding, in vivo miRNA manipulation, and FAM3A rescue with metabolic readouts

    PMID:28411267

    Open questions at the time
    • Single lab; hepatic NFE2 regulation not independently confirmed
    • Physiological relevance versus overexpression unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many post-translational, partner, and chromatin inputs are integrated to switch NF-E2 between erythroid and megakaryocytic programs—and how NF-E2 levels must fall for terminal platelet release—remains unresolved.
  • No unified model linking modification state to lineage-specific target selection
  • Mechanism requiring NFE2 downregulation for platelet release only indirectly supported (ROCK inhibition correlation)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0140110 transcription regulator activity 7
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-109582 Hemostasis 3 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 2
Partners
CREBBPFLI1ITCHMAFFMAFGMAFKRUNX1WWP1
Complex memberships
NF-E2 (p45/small Maf heterodimer)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 NFE2 (p45 NF-E2) was identified as a haematopoietic-specific basic-leucine zipper protein that dimerizes with a ubiquitous partner to form the functional NF-E2 transcription factor that binds AP-1-like recognition sites in erythroid locus control regions. cDNA cloning, biochemical characterization of dimerization and DNA binding Nature High 8469283
1994 NFE2 p45 dimerizes with small Maf proteins (MafF, MafG, MafK) to form functional NF-E2; small Maf homodimers act as negative regulators, while p45-Maf heterodimers support active transcription, establishing that erythroid transcription can be positively or negatively regulated depending on the ratio of p45 to small Maf proteins. cDNA cloning of small Maf proteins, in vitro dimerization assays, in vivo transcription assays with reporter constructs Nature High 8107826
1993 A missense mutation (V173A) in p45 NF-E2 in microcytosis (mk) mice causes impaired NF-E2 function, leading to defective globin production and iron metabolism, establishing a direct mechanistic link between p45 NF-E2 activity and both globin regulation and iron absorption. DNA sequencing of wild-type and mk alleles, expression analysis in erythroid tissues and duodenum Nature High 8469289
1993 Human NF-E2 encodes a basic leucine-zipper protein with near-identity to mouse p45 NF-E2; high NF-E2 mRNA was found in erythroleukemic cell lines, with expression also detectable in colon and testis. cDNA cloning from K562 cells, Northern blot analysis of human tissues Proceedings of the National Academy of Sciences of the United States of America Medium 8248255
1995 NF-E2 binding sites (together with GATA-1 binding motifs) are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region, as demonstrated by mutational analysis in stably transfected murine erythroleukemia cells. Site-directed mutagenesis of HS4-forming element, stable transfection into MEL cells, DNase I and micrococcal nuclease sensitivity assays The EMBO journal High 7828582
1995 Small Maf proteins (MafG, MafK, MafF) dimerize with p45 NF-E2 to regulate NF-E2 binding specificity; they also dimerize with Fos (but not Jun or v-Maf), and Fos-small Maf heterodimers cannot activate an NF-E2-site-driven promoter, suggesting Fos competes with p45 for small Maf partners to repress NF-E2 target genes. Bacterially expressed protein dimerization assays, DNA binding (EMSA), transactivation assays in transfected cells Molecular and cellular biology High 7891713
1997 p45 NF-E2 directly regulates thromboxane synthase (TXS) gene expression in megakaryocytes: the TXS promoter contains a functional NF-E2 binding site, an intronic NF-E2 site functions as a chromatin-dependent enhancer, and p45-null megakaryocytes lack TXS mRNA. In vivo chromatin immunoprecipitation/immunoselection from megakaryocytic cell line, promoter/enhancer functional assays, p45-null mouse analysis The EMBO journal High 9312024
1998 p45 NF-E2 is the only large subunit in primary megakaryocytes and dimerizes with distinct small Maf proteins; MafG and/or MafF predominate in megakaryocytes whereas MafK predominates in erythroid cells, representing the first example of differential small Maf protein expression among related blood lineages, while DNA-binding specificity is similar in both cell types. Culture of fetal liver megakaryocytes, nuclear extract preparation, electrophoretic mobility shift assay, immunoprecipitation The Journal of biological chemistry High 9516460
1998 The transactivation domain of NF-E2 p45 contains two PPXY motifs; PPXY-1 (but not PPXY-2) interacts with WW domains, including the amino-terminal WW domain of the ubiquitin ligase homologue WWP1 (expressed in hematopoietic tissues), with high affinity (KD = 5.7 nM), and mutation of PPXY-1 inhibits NF-E2 transactivation function. GST-WW domain pulldown with quantitative binding analysis, phage display peptide selection, PPXY mutagenesis with transactivation assay Biochemistry High 9753456
1998 NF-E2 DNA-binding activity and erythroid-specific gene expression in differentiating MEL cells require cAMP-dependent protein kinase (PKA); PKA-deficient MEL cells show reduced NF-E2·DNA complex formation. Although p45 and p18 are phosphorylated by PKA in vitro, this phosphorylation did not directly alter DNA binding, suggesting PKA regulates NF-E2 complex formation indirectly. Comparison of PKA-deficient vs. normal MEL cells upon HMBA-induced differentiation, EMSA, in vitro phosphorylation assay The Journal of biological chemistry Medium 7721832
1998 NF-E2 activity during erythroleukemia cell differentiation requires serine/threonine phosphorylation; activation of the Ras-Raf-MAP kinase cascade increases NF-E2 activity; overexpression of MafK suppresses NF-E2 activity not only by competing for DNA binding but also by direct transcription inhibition through its bZIP domain. Chemical inhibitor treatment (2-aminopurine, genistein), Ras-Raf pathway activation, MafK overexpression/domain analysis, DMSO-induced MEL cell differentiation The Journal of biological chemistry Medium 9478996
1999 p45 NF-E2-null mice show profound thrombocytopenia due to late arrest in megakaryocyte differentiation, with NF-E2 required for regulated megakaryocyte growth and differentiation into platelets; erythroid abnormalities (anisocytosis, hypochromia) were also confirmed to be hematopoietic cell-intrinsic by transplantation into irradiated wild-type recipients. p45 NF-E2 knockout mouse analysis, bone marrow transplantation into irradiated recipients, splenectomy experiments Blood High 10556187
2000 NF-E2 binds directly and specifically to the tandem Maf recognition elements of hypersensitive site 2 (HS2) in the beta-globin locus control region in living erythroleukemia cells and mouse fetal liver, dependent on p45 presence and intact MAREs, supporting a direct role for NF-E2 in LCR-mediated beta-globin activation. Chromatin immunoprecipitation assay in intact cells and fetal liver Blood High 10891470
2000 NF-E2 is required for expression of beta1 tubulin in megakaryocytes; beta1 tubulin mRNA and protein are virtually absent in NF-E2-deficient megakaryocytes, and restoring NF-E2 activity rescues beta1 tubulin expression. However, re-expressing beta1 tubulin alone does not restore proplatelet formation, indicating that additional NF-E2 targets are required. mRNA subtraction between normal and NF-E2-deficient megakaryocytes, rescue experiments restoring NF-E2 or beta1 tubulin in deficient cells Blood High 10942379
2001 NF-E2 complex (p45/MafK heterodimer) is recruited to the beta-globin LCR and active globin promoters during erythroid differentiation; prior to differentiation the LCR is occupied by small Maf proteins alone, and differentiation-coupled NF-E2 recruitment correlates with >100-fold increase in beta-major globin transcription without a significant change in locus-wide histone H3 acetylation. Chromatin immunoprecipitation in MEL cells before and after DMSO-induced differentiation Proceedings of the National Academy of Sciences of the United States of America High 11517325
2001 CBP acetylates MafG (the small subunit of NF-E2) predominantly in the basic region; MafG is acetylated in vivo in erythroid cells; acetylation augments NF-E2 DNA binding activity; mutations at major acetylation sites of MafG markedly reduce NF-E2 DNA binding and transcriptional activation. Both p45 and MafG interact with CBP in vitro and in vivo. Co-immunoprecipitation, in vitro acetyltransferase assay, anti-acetyl-lysine immunoprecipitation, transfection/reporter assay with acetylation-site mutants The Journal of biological chemistry High 11154691
2003 NF-E2 recruits Rab27b to the megakaryocyte/platelet lineage; normal Rab27b expression increases with terminal megakaryocyte differentiation in an NF-E2-dependent manner; ChIP demonstrates NF-E2 recruitment to the Rab27B promoter; inhibition of endogenous Rab27 function causes severe defects in proplatelet formation; Rab27b localizes to alpha and dense granules in megakaryocytes. Chromatin immunoprecipitation, expression analysis in NF-E2-deficient cells, Rab27 functional inhibition in primary megakaryocytes, subcellular localization by fluorescence microscopy Blood High 12907454
2005 p45/NF-E2 is sumoylated in vivo at lysine 368 in human erythroid K562 cells and mouse fetal liver; sumoylation enhances NF-E2 transactivation capability and DNA binding affinity; intact K368 is required for p45 binding to DNase I-hypersensitive sites of the beta-globin LCR; only wild-type p45 (not K368R mutant) rescues beta-globin expression in p45-null CB3 cells. Sumoylated p45 co-localizes with PML nuclear bodies enriched in SUMO-1 and RNA Pol II. In vitro sumoylation assay, transfection mutagenesis (K368R), ChIP, stable transfection rescue assay in p45-null cells, immunofluorescence colocalization Molecular and cellular biology High 16287851
2006 NF-E2 (p45) directly activates the LIMS1/PINCH1 gene in megakaryocytes; LIMS1 is highly expressed in megakaryocytes and platelets and significantly reduced in NF-E2-deficient cells; transactivation studies and chromatin immunoprecipitation implicate LIMS1 as a direct NF-E2 target. Genome-wide mRNA expression profiling of staged megakaryocytes, computational promoter analysis, transactivation assays, chromatin immunoprecipitation Blood Medium 17047147
2001 Human ITCH protein (ortholog of mouse Itch) interacts with p45/NF-E2 (identified by yeast two-hybrid) and acts as a transcriptional corepressor of p45/NF-E2 in transfection experiments. Yeast two-hybrid screen of human erythroleukemia cDNA library, transfection assays Genomics Medium 11318614
2009 In megakaryocytes, p45 NF-E2 competes with Nrf2 at cytoprotective gene targets (common targets), acting as a less efficacious activator to maintain moderate expression of these genes; this competition promotes ROS accumulation, which in turn enhances platelet gene expression, establishing that p45 dominates over Nrf2 to promote megakaryocytic maturation. Genome-wide gene expression profiling of p45-null vs. wild-type megakaryocytes, genetic analysis with p45/Nrf2 compound loss-of-function, ROS measurement Blood High 19901266
2010 AML1/RUNX1 directly binds the NF-E2 promoter in vivo (demonstrated by ChIP) and activates NF-E2 expression; AML1 binding to the NF-E2 promoter is increased in PV patient granulocytes; RNAi-mediated suppression of AML1 or its partner CBF-beta significantly decreases NF-E2 expression, establishing NFE2 as a direct AML1 target gene. NF-E2 promoter characterization, chromatin immunoprecipitation, RNAi knockdown of AML1/CBF-beta, expression correlation analysis Blood High 20339092
2013 Acquired truncating insertion/deletion mutations in the NF-E2 gene in MPN patients produce truncated NF-E2 proteins that enhance wild-type NF-E2 function and cause erythrocytosis and thrombocytosis in a murine model; NF-E2 mutant cells acquire a proliferative advantage with clonal dominance over wild-type NF-E2 cells. Sequencing of MPN patient samples, expression of truncated NF-E2 in murine model, clonal dominance assay The Journal of experimental medicine High 23589569
2013 p45 NF-E2 directly activates Selp (P-selectin) and Myl9 genes in megakaryocytes as established by genome-wide ChIP-seq; mice expressing a hypomorphic p45 mutant lacking the N-terminal transactivation domain show platelet hypofunction and mild thrombocytopenia, with repressed lung metastasis of melanoma cells (which requires platelet activation). ChIP-seq in primary megakaryocytes, hypomorphic p45 mutant mouse model, platelet function assays, melanoma lung metastasis assay Molecular and cellular biology High 23648484
2016 NF-E2 co-occupies late-acting enhancers (marked by H3K4me2) with FLI1 and RUNX1 in primary megakaryocytes; enhancers bound by NF-E2 together with RUNX1, FLI1, or both show the highest histone activation signals and associate best with genes activated late in megakaryocyte maturation including genes responsible for platelet assembly and release. ChIP-seq for NF-E2, FLI1, RUNX1, H3K4me2 in primary megakaryocytes; genome-wide chromatin dynamics analysis Scientific reports High 27457419
2018 The histone demethylase JMJD1C is a novel NFE2 target gene; JMJD1C in turn binds the NFE2 promoter, decreasing H3K9me2 and HP1α binding, creating an autoregulatory loop. Additionally, NFE2 is regulated through H3Y41 phosphorylation (JAK2 pathway), which inhibits HP1α binding to the NFE2 locus. ChIP in MPN patient granulocytes vs. controls, siRNA knockdown of JMJD1C, histone modification analysis (H3K9me1/me2, H3Y41ph), decitabine treatment of JAK2V617F cell lines Blood High 29519804
2017 NFE2 induces miR-423-5p expression by binding the miR-423 precursor gene promoter; miR-423-5p then represses FAM3A expression and the FAM3A-ATP-Akt pathway in hepatocytes; hepatic NFE2 overexpression upregulates miR-423-5p to promote gluconeogenesis, lipid deposition, and hyperglycemia. Reporter assay and ChIP for NFE2 binding to miR-423 promoter, miR-423-5p overexpression/inhibition in mice, FAM3A rescue experiments Diabetes Medium 28411267
1997 Human MafK and MafG form homodimers or heterodimers with p45 NF-E2 and p45-related CNC family proteins to bind NF-E2 sites; DNA binding depends on these homo- or heterodimer formations. cDNA cloning of human mafK and mafG, EMSA with recombinant proteins, dimerization assays Oncogene Medium 9150357
1998 p45 NF-E2 and Nrf2 function independently in hematopoiesis: compound p45/Nrf2 double-mutant mice show no greater failure in erythroid or megakaryocytic development than either single mutant alone, indicating that Nrf2 does not compensate for p45 deficiency in erythroid cells. Generation of p45 and Nrf2 compound knockout mice, hematological analysis Journal of biochemistry Medium 9538217
2010 USF and NF-E2 interact in erythroid cells; USF is required for efficient association of RNA Pol II with LCR templates, while USF and NF-E2 together regulate Pol II association with the adult beta-globin promoter; NF-E2 activity mediates phosphorylation of LCR-associated Pol II at serine 5 of the C-terminal domain during erythroid differentiation. Immobilized LCR template assay, ChIP, co-immunoprecipitation of USF and NF-E2, MEL cell differentiation with NF-E2 activity assay The Journal of biological chemistry Medium 20236933
2014 ROCK inhibition in megakaryocytes downregulates NFE2 expression (along with MYC) in mature megakaryocytes, and this downregulation correlates with increased proplatelet formation, suggesting that NFE2 levels must decrease for terminal platelet release. ROCK inhibitor treatment of cord blood-derived megakaryocytes, expression analysis of NFE2 and MYC, proplatelet formation assay British journal of haematology Medium 24383889
1997 NF-E2p18/MafK is required for DMSO-induced erythroid differentiation of Friend erythroleukemia cells; overexpression of MafK increases NF-E2 DNA binding activity and activates NF-E2 site-dependent transcription; antisense inhibition of MafK blocks differentiation, establishing MafK as the p18 subunit that participates in and enhances NF-E2 activity. Stable transfection of sense and antisense p18/MafK constructs, EMSA, transient transfection reporter assays, induction of differentiation Leukemia Medium 9009092
1995 Antisense inhibition of NF-E2 expression in purified hematopoietic progenitor cells selectively impairs erythroid colony formation, with NF-E2 expression preceding the erythropoietin receptor during differentiation; NF-E2 function appears restricted to erythroid differentiation and maturation. Antisense oligomers targeting NF-E2 mRNA in purified hematopoietic progenitors, colony formation assay The Journal of clinical investigation Medium 7738198
2003 Mice deficient in NF-E2 show a 200-300% increase in bone volume and formation parameters; when osteoblasts are cultured with NF-E2-deficient megakaryocytes, osteoblast proliferation increases 3- to 6-fold by a mechanism requiring cell-to-cell contact, establishing a megakaryocyte-osteoblast interaction mediated by NF-E2-deficient (immature) megakaryocytes. NF-E2 knockout mouse histomorphometry and microCT, co-culture of osteoblasts with megakaryocytes from mutant mice, contact-dependence assay Journal of bone and mineral research Medium 15005853
2007 p45 NF-E2 directly regulates megakaryocyte differentiation and platelet production; retroviral overexpression of p45-NF-E2 in murine bone marrow cells enhances megakaryocyte marker expression (CD41, CD42a, CD42b), CFU-MK formation, acetylcholinesterase+ MK numbers, and proplatelet and functional platelet production both in vitro and in vivo following transplantation. Retroviral transduction of murine bone marrow cells, colony assays, flow cytometry, transplantation into irradiated mice Experimental hematology Medium 17423245

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 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 567 8943040
2001 The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer research 564 11309284
2000 Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. Proceedings of the National Academy of Sciences of the United States of America 449 11035812
2007 GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. The Journal of biological chemistry 425 17403689
1994 Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature 418 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
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
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 220 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 196 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 177 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 160 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
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 148 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 147 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
2000 Hematopoietic-specific beta 1 tubulin participates in a pathway of platelet biogenesis dependent on the transcription factor NF-E2. Blood 133 10942379
2015 Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway. The Journal of biological chemistry 132 26013831
1995 NF-E2 and GATA binding motifs are required for the formation of DNase I hypersensitive site 4 of the human beta-globin locus control region. The EMBO journal 124 7828582
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
2001 Activation of beta-major globin gene transcription is associated with recruitment of NF-E2 to the beta-globin LCR and gene promoter. Proceedings of the National Academy of Sciences of the United States of America 115 11517325
2010 Global downstream pathway analysis reveals a dependence of oncogenic NF-E2-related factor 2 mutation on the mTOR growth signaling pathway. Cancer research 113 21062981
1995 Differential expression and functional role of GATA-2, NF-E2, and GATA-1 in normal adult hematopoiesis. The Journal of clinical investigation 113 7738198
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
2009 NF-E2 domination over Nrf2 promotes ROS accumulation and megakaryocytic maturation. Blood 93 19901266
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
2012 Dimethylfumarate attenuates renal fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. PloS one 91 23056222
2011 Nrf2b, novel zebrafish paralog of oxidant-responsive transcription factor NF-E2-related factor 2 (NRF2). The Journal of biological chemistry 90 22174413
2000 Direct interaction of NF-E2 with hypersensitive site 2 of the beta-globin locus control region in living cells. Blood 90 10891470
1999 Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2. Blood 85 10556187
2013 Attenuation of β-amyloid-induced oxidative cell death by sulforaphane via activation of NF-E2-related factor 2. Oxidative medicine and cellular longevity 80 23864927
2017 NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes 79 28411267
2013 Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-related factor (Nrf2) in cultured motor neurons. International journal of molecular sciences 79 23574943
2001 Stimulation of NF-E2 DNA binding by CREB-binding protein (CBP)-mediated acetylation. The Journal of biological chemistry 79 11154691
2003 A role for Rab27b in NF-E2-dependent pathways of platelet formation. Blood 78 12907454
1997 p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. The EMBO journal 77 9312024
2018 Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway. Free radical biology & medicine 76 30342186
2002 Activation of mouse Pi-class glutathione S-transferase gene by Nrf2(NF-E2-related factor 2) and androgen. The Biochemical journal 74 12023900
1998 The NF-E2 transcription factor. The international journal of biochemistry & cell biology 74 9675875
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
2016 Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer. Oncotarget 71 27323826
2009 NF-E2-related factor 2 regulates the stress response to UVA-1-oxidized phospholipids in skin cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 19720622
2013 MPN patients harbor recurrent truncating mutations in transcription factor NF-E2. The Journal of experimental medicine 68 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
1993 Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2. Nature 62 8469289
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 60 23043106
2006 Hepatic ischemia-reperfusion induces renal heme oxygenase-1 via NF-E2-related factor 2 in rats and mice. Molecular pharmacology 59 17151289
1998 Physical and functional interactions between the transactivation domain of the hematopoietic transcription factor NF-E2 and WW domains. Biochemistry 59 9753456
1998 Characterization of the hematopoietic transcription factor NF-E2 in primary murine megakaryocytes. The Journal of biological chemistry 56 9516460
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 52 28224478
2011 Epigallocatechin-gallate stimulates NF-E2-related factor and heme oxygenase-1 via caveolin-1 displacement. The Journal of nutritional biochemistry 51 21447442
2006 Expression analysis of primary mouse megakaryocyte differentiation and its application in identifying stage-specific molecular markers and a novel transcriptional target of NF-E2. Blood 50 17047147
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 48 17676812
2015 Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells. Cellular and molecular life sciences : CMLS 46 25721735
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 45 26116522
2013 Developmental expression of the Nfe2-related factor (Nrf) transcription factor family in the zebrafish, Danio rerio. PloS one 45 24298298
1993 Single-copy transduction and expression of human gamma-globin in K562 erythroleukemia cells using recombinant adeno-associated virus vectors: the effect of mutations in NF-E2 and GATA-1 binding motifs within the hypersensitivity site 2 enhancer. Blood 45 8400240
2010 Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta pharmacologica Sinica 44 21151161
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 43 29742982
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 42 35212366
2014 Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages. British journal of pharmacology 42 24116971
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 42 23526214
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
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 41 23673813
2000 Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL-1beta on megakaryocytopoiesis and NF-E2 expression. British journal of haematology 41 11091227
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
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
1998 Ablation of Nrf2 function does not increase the erythroid or megakaryocytic cell lineage dysfunction caused by p45 NF-E2 gene disruption. Journal of biochemistry 36 9538217
2019 Apigenin Protects Against Renal Tubular Epithelial Cell Injury and Oxidative Stress by High Glucose via Regulation of NF-E2-Related Factor 2 (Nrf2) Pathway. Medical science monitor : international medical journal of experimental and clinical research 35 31309931
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
2010 USF and NF-E2 cooperate to regulate the recruitment and activity of RNA polymerase II in the beta-globin gene locus. The Journal of biological chemistry 31 20236933
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
2014 Tryptanthrin protects hepatocytes against oxidative stress via activation of the extracellular signal-regulated kinase/NF-E2-related factor 2 pathway. Biological & pharmaceutical bulletin 30 25273386
2016 NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes. Scientific reports 29 27457419
2022 Chlorogenic Acid, the Main Antioxidant in Coffee, Reduces Radiation-Induced Apoptosis and DNA Damage via NF-E2-Related Factor 2 (Nrf2) Activation in Hepatocellular Carcinoma. Oxidative medicine and cellular longevity 28 35958020
2004 Interleukin-1beta up-regulates the expression of thrombopoietin and transcription factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells. The Journal of laboratory and clinical medicine 28 14966463
2007 NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo. Experimental hematology 27 17923245
2018 Amentoflavone-induced oxidative stress activates NF-E2-related factor 2 via the p38 MAP kinase-AKT pathway in human keratinocytes. The international journal of biochemistry & cell biology 26 29627441
1997 NF-E2p18/mafK is required in DMSO-induced differentiation of Friend erythroleukemia cells by enhancing NF-E2 activity. Leukemia 26 9009092
2020 NF-E2-Related Factor 2 Regulates Interferon Receptor Expression and Alters Macrophage Polarization in Lupus. Arthritis & rheumatology (Hoboken, N.J.) 25 32500632
2013 NF-E2 p45 is important for establishing normal function of platelets. Molecular and cellular biology 25 23648484
2010 NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription. Cellular and molecular life sciences : CMLS 25 20309604
2005 Sumoylation of p45/NF-E2: nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus. Molecular and cellular biology 25 16287851
2001 Human ITCH is a coregulator of the hematopoietic transcription factor NF-E2. Genomics 25 11318614
1995 cAMP-dependent protein kinase is necessary for increased NF-E2.DNA complex formation during erythroleukemia cell differentiation. The Journal of biological chemistry 24 7721832

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