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Showing NFE2L3 — NRF3 is a alias.

NFE2L3

Nuclear factor erythroid 2-related factor 3 · UniProt Q9Y4A8

Length
694 aa
Mass
76.2 kDa
Annotated
2026-06-10
62 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NFE2L3/NRF3 is a CNC-family bZIP transcription factor that heterodimerizes with small Maf proteins (MafK, MAFG) to bind antioxidant/Maf recognition elements (ARE/MARE) and regulate transcription, functioning as a context-dependent controller of proteasome homeostasis, redox balance, cell differentiation, and tumor biology (PMID:10037736, PMID:15388789, PMID:31628195). Its activity is set largely by stringent post-translational control: NRF3 is an N-glycosylated protein targeted to the ER through an N-terminal NHB1 tripartite signal peptide, processed to mature ~90/80-kDa isoforms that distribute between the nuclear envelope and nucleoplasm, with ER stressors (tunicamycin, brefeldin A) triggering its activation (PMID:17976382, PMID:19047052). Under basal conditions NRF3 is rapidly degraded—cytoplasmically by the ERAD ligase HRD1 with VCP, and in the nucleus by SCF adaptors (β-TRCP, and FBW7 following GSK3 phosphorylation)—while the aspartic protease DDI2 enables its nuclear translocation (PMID:26306035, PMID:28970512). As a transcription factor NRF3 acts as a direct repressor of NQO1 (PMID:15385560) and a direct activator of POMP, driving ubiquitin-independent 20S proteasome assembly to degrade the tumor suppressors p53 and Rb (PMID:32123008); it further controls a proteasome program in concert with NFE2L1, which it represses translationally by inducing CPEB3 (PMID:32366381). Across tissues NRF3 directs distinct programs: it promotes smooth muscle differentiation via myocardin and Pla2g7 (PMID:20093628, PMID:22247257), coordinates melanogenesis (PMID:36640303), drives cardiomyocyte apoptosis after infarction by recruiting hnRNPK and DNMT1 to methylate and silence the Pitx2 promoter (PMID:40099370), and promotes injury-induced neointimal hyperplasia by transactivating Trim5 downstream of ATF4/ER stress (PMID:40377016). In cancer NRF3 is both oncogenic and tumor-suppressive depending on context—promoting proliferation through targets such as UHMK1, PIK3CA, IL33, and mTORC1-pathway genes (PMID:28970512, PMID:37720674, PMID:35091681, PMID:36818298), yet suppressing squamous carcinogenesis through interaction with HSPA5/GRP78 (PMID:37807968).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Established the fundamental molecular identity of NRF3 as a CNC-bZIP factor that requires small Maf heterodimerization to bind DNA and activate transcription.

    Evidence In vitro transcription/translation, EMSA, co-IP, and transactivation assays on the chicken beta-globin MARE

    PMID:10037736

    Open questions at the time
    • Endogenous target genes not yet defined
    • No data on regulation of NRF3 activity or localization
  2. 2004 High

    Defined NRF3 as functionally bidirectional—a repressor at the NQO1 ARE yet bearing a strong activation domain—answering whether a CNC factor can negatively regulate ARE genes.

    Evidence Overexpression/RNAi in HepG2 and JAR cells, EMSA/supershift, domain deletion, MAFG yeast two-hybrid and TNF-alpha induction

    PMID:15385560 PMID:15388789

    Open questions at the time
    • Mechanism distinguishing repressed vs activated targets unresolved
    • Signals controlling activation domain usage unknown
  3. 2008 High

    Resolved how NRF3 is spatially controlled, showing it is an ER-targeted N-glycoprotein whose NHB1 signal peptide governs processing, isoform distribution, and ER-stress responsiveness.

    Evidence Signal-peptide mutagenesis, subcellular fractionation, glycosidase assays, and ER-stress induction (extending CHX-chase/MG-132 findings)

    PMID:17976382 PMID:19047052

    Open questions at the time
    • Protease/machinery releasing NRF3 from ER not identified at this stage
    • Functional consequence of each isoform unclear
  4. 2015 High

    Identified a nuclear degradation route, showing GSK3 phosphorylation primes NRF3 for SCF-FBW7 ubiquitination and relieves ARE repression.

    Evidence Co-IP, ubiquitination and kinase assays, FBW7 dimerization mutants, NQO1-ARE reporter

    PMID:26306035

    Open questions at the time
    • Stimuli regulating GSK3-FBW7 axis on NRF3 not defined
    • Relationship to ER-associated degradation not yet integrated
  5. 2017 High

    Unified NRF3 turnover into compartment-specific pathways and identified DDI2 as the protease enabling nuclear translocation, while linking NRF3 to proliferation via UHMK1.

    Evidence Co-IP, ubiquitination assays, DDI2 knockdown, fractionation, expression profiling, proliferation assays

    PMID:28970512

    Open questions at the time
    • Trigger activating DDI2-dependent release unknown
    • Direct vs indirect UHMK1 regulation not fully resolved
  6. 2020 High

    Defined NRF3's central role in proteasome homeostasis—directly inducing POMP for ubiquitin-independent 20S assembly to degrade p53/Rb, and repressing NFE2L1 translation through CPEB3.

    Evidence ChIP, pharmacological dissection (bortezomib vs TAK-243), xenografts, polysome profiling, RIP, double knockdown proteasome assays

    PMID:32123008 PMID:32366381

    Open questions at the time
    • Conditions favoring proteasome induction vs other programs unclear
    • In vivo p53/Rb degradation contribution not quantified
  7. 2019 High

    Placed NRF3 within oncogenic signaling networks, showing it is induced by NF-kB (RELA) and Wnt/β-catenin-TCF4 and feeds proliferative outputs in colon cancer.

    Evidence ChIP, reporter assays, siRNA/shRNA, Apc-deficient organoids/intestine, xenografts (with genome-wide ChIP-exo defining NRF3-specific targets)

    PMID:31288376 PMID:31628195 PMID:31693889

    Open questions at the time
    • Integration of upstream NF-kB/Wnt inputs with ER-anchored regulation unclear
    • Tissue specificity of the 22-gene NRF3 program not mapped
  8. 2018 High

    Established physiological roles in adhesion and stress-induced apoptosis, with Nrf3 promoting apoptosis by suppressing integrin-mediated adhesion signaling in keratinocytes.

    Evidence Nrf3 KO mice, primary keratinocytes, UV/oxidative stress, integrin flow cytometry, FAK western blot, motility assays

    PMID:29487353

    Open questions at the time
    • Direct transcriptional targets controlling integrins not defined
    • Link to ARE/Maf dimerization in this context untested
  9. 2023 Medium

    Demonstrated NRF3 can be tumor-suppressive through a non-transcriptional protein interaction, binding HSPA5/GRP78 to restrain squamous carcinogenesis.

    Evidence IP-MS interactome, NRF3-KO skin carcinogenesis model, 3D invasion, xenografts, HSPA5 rescue

    PMID:37807968

    Open questions at the time
    • Reciprocal validation of the HSPA5 interaction limited
    • Context determining oncogenic vs suppressive role unresolved
  10. 2025 High

    Extended NRF3 into cardiovascular pathology, showing epigenetic and autophagic mechanisms—hnRNPK/DNMT1-mediated Pitx2 silencing driving cardiomyocyte apoptosis, and ATF4-induced NRF3 transactivating Trim5 to drive neointimal hyperplasia.

    Evidence Global and cell-specific KO mice, ChIP-seq, IP-MS, mitochondrial ROS assays, AAV rescue, porcine stenting model, ChIP

    PMID:40099370 PMID:40377016

    Open questions at the time
    • Signals selecting epigenetic-repressor vs activator mode unknown
    • Generalizability of hnRNPK/DNMT1 recruitment to other targets untested
  11. 2025 Medium

    Revealed that NRF3 abundance is itself set by mRNA modifications (METTL3 m6A, NAT10 ac4C) that stabilize NFE2L3 transcript and feed Wnt/AKT stemness programs in cancer.

    Evidence m6A-RIP, acRIP-seq, RNA stability assays, ChIP-seq (LASP1), knockdown/overexpression, xenografts

    PMID:40169553 PMID:40249818

    Open questions at the time
    • Physiological triggers of these RNA modifications unclear
    • Interplay with protein-level ERAD/FBW7 control not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular switch dictates whether NRF3 acts as a transcriptional activator, an ARE repressor, an epigenetic silencer via hnRNPK/DNMT1, or a tumor suppressor via HSPA5 in a given cell context remains unresolved.
  • No unifying model linking upstream stimulus to choice of target program
  • Determinants of oncogenic vs tumor-suppressive output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 6
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005634 nucleus 2 GO:0005635 nuclear envelope 1 GO:0005654 nucleoplasm 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
DDI2DNMT1FBW7HNRNPKHRD1MAFGMAFKVCP

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Nrf3 heterodimerizes with MafK and the resulting complex binds to the Maf recognition element (MARE) in the chicken beta-globin enhancer and activates transcription, establishing Nrf3 as a CNC-family bZIP transcription factor that functions through small Maf protein heterodimerization. In vitro transcription/translation, EMSA (bandshift), co-immunoprecipitation, transfection-based transcriptional activation assays The Journal of biological chemistry High 10037736
2004 Nrf3 associates with small Maf proteins to bind the antioxidant response element (ARE) and acts as a negative regulator of ARE-mediated NQO1 gene expression; repression requires the heterodimerization and DNA-binding domains but not the transcriptional activation domain. RNAi knockdown of Nrf3 increases NQO1 expression, confirming endogenous repressive function. Overexpression in HepG2 cells, deletion mutant analysis, EMSA/supershift assays with in vitro-translated proteins and nuclear extracts, immunoprecipitation, RNA interference The Journal of biological chemistry High 15385560
2004 Human NRF3 dimerizes with MAFG in vivo (yeast two-hybrid and transfection confirmation), and the NRF3/MAFG heterodimer recognizes NF-E2/MARE-type DNA motifs; a strong transcriptional activation domain was mapped to the central region of the NRF3 protein. NRF3 transcript and protein levels are induced by TNF-alpha in JAR choriocarcinoma cells. Yeast two-hybrid screen, transfection co-expression, EMSA, deletion mapping of transcriptional activation domain, TNF-alpha induction with RT-PCR and western blot Molecular endocrinology High 15388789
2007 Nrf3 is subject to rapid proteasomal degradation (stabilized by MG-132) and is N-glycosylated, representing the first identification of a post-translational modification of Nrf3; Nrf3 associates with the endoplasmic reticulum. Cycloheximide chase, proteasome inhibitor (MG-132) treatment, N-glycosylation analysis, cellular fractionation/ER association assays FEBS letters Medium 17976382
2008 Nrf3 is targeted to the ER through its N-terminal NHB1 sequence, which functions as a tripartite signal peptide (n, h, c regions). The h region (residues 12–23) directs ER targeting and is required for Asn glycosylation; the c region (residues 24–39) contains a signal peptidase cleavage site generating the ~90-kDa mature glycoprotein from a ~96-kDa precursor. The ~90- and ~80-kDa isoforms localize to the nuclear envelope and the ~70-kDa (non-glycated) isoform to the nucleoplasm. ER stressors tunicamycin and brefeldin A activate Nrf3, and NHB1 is required for this response. Deletion and point mutants expressed in cells, subcellular fractionation, western blot, glycosylation analysis (glycosidase treatment), ER stress induction The Journal of biological chemistry High 19047052
2010 Nrf3 is required for smooth muscle cell (SMC) differentiation from embryonic stem cells. Nrf3 overexpression dose-dependently enhances SMC differentiation and upregulates the SMC-specific transcription factor myocardin (but not SRF). Nrf3 directly binds to promoters of SMC differentiation genes (ChIP). Nrf3 overexpression enhances NADPH oxidase-dependent ROS production and inhibits antioxidant signaling, and Nrf3 is involved in ER stressor-induced SMC differentiation. Knockdown and overexpression in ESC differentiation model, qRT-PCR/western blot for markers, chromatin immunoprecipitation (ChIP), NADPH oxidase/ROS assays Circulation research High 20093628
2012 Nrf3 directly binds to the promoter regions of the Pla2g7 (platelet-activating factor acetylhydrolase) gene and regulates its expression; Pla2g7 activity mediates SRF binding to SMC differentiation gene promoters and is required for SMC differentiation, placing Nrf3 upstream of Pla2g7 in a pathway controlling vascular smooth muscle differentiation. ChIP assay, promoter reporter assay, knockdown/overexpression of Pla2g7 and Nrf3 in ESC differentiation model, enzymatic activity assay, ROS measurements Arteriosclerosis, thrombosis, and vascular biology Medium 22247257
2015 NFE2L3 is ubiquitinated and degraded via the SCF-FBW7 E3 ubiquitin ligase complex. GSK3 phosphorylates NFE2L3 and this phosphorylation is required for FBW7-dependent ubiquitination and degradation. Dimerization of FBW7 is required for NFE2L3 degradation. FBW7 abrogates NFE2L3-mediated repression of the NQO1 ARE. Co-immunoprecipitation, ubiquitination assay, kinase assay (GSK3 phosphorylation), FBW7 mutant overexpression, NQO1-ARE reporter assay The Journal of biological chemistry High 26306035
2017 Under basal conditions NRF3 is rapidly degraded in the cytoplasm by the ER-associated degradation (ERAD) ubiquitin ligase HRD1 and VCP (valosin-containing protein). Nuclear NRF3 is separately degraded by β-TRCP, an adaptor for the SCF ubiquitin ligase. Nuclear translocation of NRF3 from the ER requires the aspartic protease DDI2 but does not require inhibition of HRD1-VCP-mediated degradation. NRF3 induces expression of UHMK1 (U2AF homology motif kinase 1) to promote cell proliferation. Co-immunoprecipitation, ubiquitination assays, proteasome inhibitor experiments, DDI2 knockdown, subcellular fractionation, gene expression profiling, cell proliferation assays Scientific reports High 28970512
2019 NRF3 specifically enhances assembly of the 20S proteasome by directly inducing transcription of POMP (proteasome maturation protein chaperone), leading to ubiquitin-independent proteolysis of the tumor suppressors p53 and Rb, thereby promoting cancer cell proliferation, tumorigenesis, and metastasis. ChIP assay (NRF3 binding to POMP promoter), siRNA knockdown, protein stability assay with 20S proteasome inhibitor (bortezomib) vs. E1 inhibitor (TAK-243), western blot for p53/Rb, cell viability assays, xenograft tumor models Molecular and cellular biology High 32123008
2019 The RELA subunit of NF-κB directly regulates NFE2L3 expression in colon cancer cells. NFE2L3 knockdown increases levels of DUX4, which functions as a direct CDK1 inhibitor, thereby decreasing colon cancer cell proliferation in vitro and tumor growth in vivo. ChIP assay, siRNA/shRNA knockdown, luciferase reporter assay, cell proliferation assays, xenograft mouse model Cell reports High 31693889
2019 The β-catenin/TCF4 complex directly binds a conserved WRE (TCF/LEF consensus element) in the NRF3 gene promoter and induces NRF3 expression in colon cancer cells. NRF3 activation in turn promotes cell proliferation and GLUT1 expression. ChIP assay (β-catenin/TCF4 binding to NRF3 WRE), reporter assay, NRF3 expression in Apc-deficient mouse intestine and organoids, qRT-PCR, western blot International journal of molecular sciences High 31288376
2020 NFE2L3 and NFE2L1 complementarily maintain basal proteasome activity in cancer cells. NFE2L3 represses NFE2L1 translation by inducing CPEB3, which binds the 3' UTR of NFE2L1 mRNA and reduces polysome formation on it. Double knockdown of NFE2L1 and NFE2L3 impairs basal proteasome activity and reduces expression of seven proteasome-related genes (PSMB3, PSMB7, PSMC2, PSMD3, PSMG2, PSMG3, POMP). Double siRNA knockdown, polysome profiling, RIP (RNA immunoprecipitation for CPEB3 binding to NFE2L1 3' UTR), proteasome activity assays, western blot Molecular and cellular biology High 32366381
2018 Nrf3-deficient keratinocytes exhibit stronger cell-cell and cell-matrix adhesion with higher cell-surface integrin levels, enhanced focal adhesion kinase (FAK) activation, more and larger focal adhesions, and higher motility, and are protected from UV- and oxidative stress-induced apoptosis in vitro and in vivo, demonstrating that Nrf3 promotes apoptosis by suppressing integrin-mediated cell adhesion signaling. Nrf3 KO mouse model, primary keratinocyte culture, UV/oxidative stress treatment, integrin surface expression (flow cytometry), FAK phosphorylation (western blot), focal adhesion staining, live-cell motility assay Cell death and differentiation High 29487353
2022 NFE2L3 directly binds the regulatory sequences of IL33 and RAB27A loci in human colorectal carcinoma cells (validated by ChIP), and its loss reduces IL33 transcript levels and modulates mast cell numbers and immune checkpoint marker expression in the tumor microenvironment. ChIP assay, Nfe2l3-/- mouse model with colitis-cancer protocol, toluidine blue staining for mast cells, RNA-seq/CIBERSORT, CD3/FOXP3 immunostaining Oncogene Medium 35091681
2023 NRF3 activates mTORC1 in cancer cells in an arginine-dependent manner by inducing expression of SLC38A9 and RagC for lysosomal mTORC1 recruitment, as well as RAB5-mediated macropinocytosis and SLC7A1-mediated arginine transport for arginine loading into lysosomes. Inhibition of the NRF3-mTORC1 axis impairs mitochondrial function and leads to cancer cell apoptosis. siRNA knockdown, mTORC1 activity assays, amino acid stimulation experiments, ChIP (NRF3 binding to target gene promoters), metabolomics, cell viability assays iScience Medium 36818298
2023 NFE2L3 promotes HCC cell proliferation by acting as a transcription factor that directly induces expression of proteasome subunit genes and ISG15, enhancing proteasome-dependent degradation of ISGylated p53; ISGylation of p53 reduces p53 stability and facilitates HCC cell growth. ChIP assay, knockdown/overexpression, proteasome activity assay, western blot for ISGylated p53, cell proliferation assays Cancer science Medium 37350063
2022 Nrf3 coordinates the melanogenesis cascade by upregulating the core melanogenic gene circuit (Mitf, Tyr, Tyrp1, Pmel, Oca2) and inducing Cln3 for melanin precursor uptake via macropinocytosis, as well as Ulk2 and Gabarapl2 for autophagosome-mediated melanosome formation and autolysosomal melanosome degradation. The HIV-1 protease inhibitor nelfinavir suppresses this Nrf3-mediated melanin production. siRNA knockdown, ChIP assay (Nrf3 binding to target promoters), macropinocytosis assay, autophagy/autolysosome assays, melanin production quantification, pharmacological inhibitor (nelfinavir) Cell reports High 36640303
2023 NRF3 suppresses squamous carcinogenesis and its tumor-suppressive effect involves interaction with HSPA5 (GRP78/BiP), a key regulator of the unfolded protein response. NRF3 deficiency increases HSPA5 levels, which promotes cancer cell survival and migration; pharmacological or knockdown inhibition of HSPA5 rescues the malignant phenotypes of NRF3-deficient SCC cells. Immunoprecipitation-mass spectrometry (NRF3 interactome), NRF3-KO mouse skin carcinogenesis model, 3D invasion assay, xenograft, HSPA5 knockdown/inhibitor rescue experiments EMBO molecular medicine Medium 37807968
2025 Nrf3 promotes cardiomyocyte apoptosis and impairs cardiac function after myocardial infarction by increasing mitochondrial ROS production through suppression of Pitx2 expression. Mechanistically, Nrf3 binds to the Pitx2 promoter and recruits hnRNPK and DNMT1 to increase DNA methylation and thereby inhibit Pitx2 transcription. Global and CM-specific Nrf3 KO mice (MI/I-R injury models), ChIP-seq (Nrf3 at Pitx2 promoter), IP-mass spectrometry (Nrf3 interactors: hnRNPK, DNMT1), mitochondrial ROS measurement, AAV-mediated CM-specific overexpression/knockdown, MitoParaquat rescue experiment, cardiac function analysis Circulation High 40099370
2025 Nrf3 promotes VSMC proliferation, migration, and inflammatory response leading to neointimal hyperplasia after vascular injury. Mechanistically, ER stress activates Nrf3 expression via ATF4. Nrf3 transcriptionally upregulates Trim5, which in turn enhances autophagy in VSMCs to drive dysfunction and injury-induced neointimal hyperplasia. Nrf3-/- and VSMC-specific Nrf3-KO mice (wire injury model), porcine carotid stenting model, ChIP assay (Nrf3 binding to Trim5 promoter), transcriptomics, rescue by Nrf3/Trim5 re-expression, Nrf3 inhibitor perivascular delivery Cardiovascular research High 40377016
2025 METTL3-mediated N6-methyladenosine (m6A) modification stabilizes NFE2L3 mRNA, increasing NFE2L3 protein levels, which in turn activates the WNT signaling pathway to maintain cancer stem cell (OV6+) stemness in lung adenocarcinoma. m6A-RIP, RNA stability assays, METTL3 knockdown/overexpression, western blot, reporter assays, xenograft models Science advances Medium 40249818
2025 NAT10-mediated ac4C acetylation of NFE2L3 mRNA promotes its stability. NFE2L3 then acts as a transcription factor that directly induces LASP1 expression (shown by ChIP-seq), activating the AKT/GSK3β/β-catenin signaling axis in clear cell renal cell carcinoma. acRIP-seq, RIP, RNA stability assay, dual luciferase reporter, ChIP-seq (NFE2L3 at LASP1 locus), NAT10 knockdown/overexpression, xenograft model Cell death & disease Medium 40169553
2019 ChIP-exo sequencing defined 22 genes transcriptionally regulated specifically by NRF3 in U2OS cells, distinct from the larger NRF1 and NRF2 target sets, with all three NRFs binding ARE motifs but with different flanking sequence preferences (NRF2 prefers GC-rich flanks; NRF1 prefers AT-rich flanks). ChIP-exo sequencing combined with RNA-seq in U2OS cells expressing each NRF member The Journal of biological chemistry Medium 31628195
2021 NFE2L3 promotes mevalonate/cholesterol biosynthesis by inducing SREBP2 and HMGCR gene expression, reduces intracellular levels of neural fatty acids by inducing GGPS1, and promotes macropinocytosis for cholesterol uptake by inducing RAB5 gene expression. ChIP assay, gene expression analysis (qRT-PCR/western blot), macropinocytosis assay, lipid metabolomics (referenced from prior studies summarized in the review) International journal of molecular sciences Low 34884489
2022 NFE2L3 directly binds the promoter region of IL-6 and transcriptionally regulates IL-6 expression, thereby promoting radioresistance in esophageal squamous cell carcinoma cells via IL-6/STAT3 signaling. Dual luciferase reporter gene assay, RNA-seq, qRT-PCR, western blot, clonogenic survival assay, xenograft radiosensitivity model Computer methods and programs in biomedicine Medium 36108571
2023 Nrf3 directly binds the p110α (PIK3CA) promoter and activates PI3K/AKT/mTOR signaling to promote proliferation and migration of triple-negative breast cancer cells. Luciferase reporter assay, ChIP assay, PI3K inhibitor rescue experiment, overexpression/knockdown studies, xenograft model Oncology letters Medium 37720674
2019 NRF3 inhibited breast cancer cell proliferation and metastasis at least in part by inactivating the AKT signaling pathway, reducing ID3 expression; exogenous ID3 expression reversed NRF3's inhibitory effects on invasion. NRF3 overexpression/silencing, western blot for AKT phosphorylation and ID3, Transwell invasion assay, MTT/colony formation assay OncoTargets and therapy Low 31114245
2026 NFE2L3 protein binds the promoter region of BHLHE40 and directly regulates its transcriptional activity in TNBC cells; NFE2L3 regulates BHLHE40 at both transcriptional and translational levels, and BHLHE40 requires NFE2L3 for cell proliferation and migration. Luciferase reporter assay, siRNA/plasmid transfection, qRT-PCR, western blot, cell proliferation and migration assays Oncology research Medium 41613788
2048 NFE2L3 protein is mutually regulated with VCP (valosin-containing protein): VCP knockdown dramatically increases NRF3 protein expression, and NRF3 overexpression reciprocally decreases VCP expression. NRF3 protein promotes ROS accumulation and inhibits ERK phosphorylation to suppress TNBC cell metastasis. Co-expression western blot, siRNA knockdown, flow cytometry (ROS), Transwell assay, NAC (ROS scavenger) rescue experiment Histology and histopathology Low 39005145
2025 NFE2L3 regulates colitis-related gene expression in vivo: Nfe2l3-/- mice show reduced DSS-induced upregulation of Stat1, Hmox1, and Slc7a11 proteins, and elevated basal pSTAT1 and SLC7A11, consistent with NFE2L3 priming a pro-inflammatory state. ENCODE ChIP data (MAFF and MAFK binding partners) support NFE2L3 binding near these loci. Nfe2l3-/- mouse DSS colitis model, histological analysis, qRT-PCR, western blot, cross-reference with ENCODE ChIP data Biochimica et biophysica acta. Molecular cell research Low 40360021

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Molecular cloning and functional characterization of a new Cap'n' collar family transcription factor Nrf3. The Journal of biological chemistry 252 10037736
2004 Nrf3 negatively regulates antioxidant-response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. The Journal of biological chemistry 92 15385560
2011 NFE2L3 (NRF3): the Cinderella of the Cap'n'Collar transcription factors. Cellular and molecular life sciences : CMLS 89 21687990
2004 Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus. Molecular and cellular biology 85 15060151
2010 Crucial role of nrf3 in smooth muscle cell differentiation from stem cells. Circulation research 81 20093628
2019 NFE2L3 Controls Colon Cancer Cell Growth through Regulation of DUX4, a CDK1 Inhibitor. Cell reports 72 31693889
2019 Differential and overlapping targets of the transcriptional regulators NRF1, NRF2, and NRF3 in human cells. The Journal of biological chemistry 69 31628195
2017 Multiple regulatory mechanisms of the biological function of NRF3 (NFE2L3) control cancer cell proliferation. Scientific reports 68 28970512
2008 The Nrf3 transcription factor is a membrane-bound glycoprotein targeted to the endoplasmic reticulum through its N-terminal homology box 1 sequence. The Journal of biological chemistry 64 19047052
2020 Defining the Functional Targets of Cap'n'collar Transcription Factors NRF1, NRF2, and NRF3. Antioxidants (Basel, Switzerland) 58 33096892
2012 Nrf3-Pla2g7 interaction plays an essential role in smooth muscle differentiation from stem cells. Arteriosclerosis, thrombosis, and vascular biology 54 22247257
2010 Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma. Blood 43 21148084
2020 NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression. Molecular and cellular biology 42 32366381
2007 Endoplasmic reticulum association and N-linked glycosylation of the human Nrf3 transcription factor. FEBS letters 40 17976382
2004 Functional and placental expression analysis of the human NRF3 transcription factor. Molecular endocrinology (Baltimore, Md.) 40 15388789
2020 NRF3-POMP-20S Proteasome Assembly Axis Promotes Cancer Development via Ubiquitin-Independent Proteolysis of p53 and Retinoblastoma Protein. Molecular and cellular biology 39 32123008
2020 NFE2L3 promotes malignant behavior and EMT of human hepatocellular carcinoma (HepG2) cells via Wnt/β‑catenin pathway. Journal of Cancer 39 33123284
2019 β-Catenin/TCF4 Complex-Mediated Induction of the NRF3 (NFE2L3) Gene in Cancer Cells. International journal of molecular sciences 38 31288376
2020 Roles of NRF3 in the Hallmarks of Cancer: Proteasomal Inactivation of Tumor Suppressors. Cancers 36 32962187
2019 New addiction to the NRF2-related factor NRF3 in cancer cells: Ubiquitin-independent proteolysis through the 20S proteasome. Cancer science 35 31742837
2025 Nrf3-Mediated Mitochondrial Superoxide Promotes Cardiomyocyte Apoptosis and Impairs Cardiac Functions by Suppressing Pitx2. Circulation 32 40099370
2019 NRF3 suppresses breast cancer cell metastasis and cell proliferation and is a favorable predictor of survival in breast cancer. OncoTargets and therapy 29 31114245
2022 Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment. Oncogene 27 35091681
2015 Stringent Control of NFE2L3 (Nuclear Factor, Erythroid 2-Like 3; NRF3) Protein Degradation by FBW7 (F-box/WD Repeat-containing Protein 7) and Glycogen Synthase Kinase 3 (GSK3). The Journal of biological chemistry 25 26306035
2021 MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3. Frontiers in oncology 22 34926237
2018 Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion. Cell death and differentiation 22 29487353
2019 NFE2L3 Inhibition Induces Cell Cycle Arrest at the G0/G1 Phase in Colorectal Cancer Cells through Downregulating CCND1 and pRb1-ser807/811. Disease markers 16 31191746
2023 NFE2L3 drives hepatocellular carcinoma cell proliferation by regulating the proteasome-dependent degradation of ISGylated p53. Cancer science 14 37350063
2023 NRF3 activates mTORC1 arginine-dependently for cancer cell viability. iScience 13 36818298
2005 The cap 'n' collar family member NF-E2-related factor 3 (Nrf3) is expressed in mesodermal derivatives of the avian embryo. The International journal of developmental biology 12 15906252
2021 Nrf3 Promotes 5-FU Resistance in Colorectal Cancer Cells via the NF-κB/BCL-2 Signaling Pathway In Vitro and In Vivo. Journal of oncology 11 34795760
2021 Pathophysiological Potentials of NRF3-Regulated Transcriptional Axes in Protein and Lipid Homeostasis. International journal of molecular sciences 11 34884489
2021 Elevated expression of NFE2L3 promotes the development of gastric cancer through epithelial-mesenchymal transformation. Bioengineered 10 34783304
2023 NRF3 suppresses squamous carcinogenesis, involving the unfolded protein response regulator HSPA5. EMBO molecular medicine 9 37807968
2022 The CNC-family transcription factor Nrf3 coordinates the melanogenesis cascade through macropinocytosis and autophagy regulation. Cell reports 9 36640303
2021 miR-23b-3p Inhibits the Oncogenicity of Colon Adenocarcinoma by Directly Targeting NFE2L3. Journal of oncology 9 34966429
2019 Nuclear factor-erythroid 2-related factor 3 (NRF3) is low expressed in colorectal cancer and its down-regulation promotes colorectal cancer malignance through activating EGFR and p38/MAPK. American journal of cancer research 9 30949407
2025 NAT10 promotes the progression of clear cell renal cell carcinoma by regulating ac4C acetylation of NFE2L3 and activating AKT/GSK3β signaling pathway. Cell death & disease 7 40169553
2024 Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo. Experimental neurology 7 38395216
2024 NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis. Cancer biology & therapy 7 39443820
2023 Nrf3 promotes the proliferation and migration of triple‑negative breast cancer by activating PI3K/AKT/mTOR and epithelial‑mesenchymal transition. Oncology letters 7 37720674
2025 A METTL3-NFE2L3 axis mediates tumor stemness and progression in lung adenocarcinoma. Science advances 5 40249818
2023 Hypomethylation-Mediated Upregulation of NFE2L3 Promotes Malignant Phenotypes of Clear Cell Renal Cell Carcinoma Cells. Molecular biotechnology 5 37071304
2022 Multi-Omics Analysis of Molecular Characteristics and Carcinogenic Effect of NFE2L3 in Pan-Cancer. Frontiers in genetics 5 35846126
2022 Transcription factor NFE2L3 promotes the proliferation of esophageal squamous cell carcinoma cells and causes radiotherapy resistance by regulating IL-6. Computer methods and programs in biomedicine 5 36108571
2022 NFE2L3 as a Potential Functional Gene Regulating Immune Microenvironment in Human Kidney Cancer. BioMed research international 5 36337840
2024 NRF3 suppresses the metastasis of triple-negative breast cancer cells by inhibiting ERK activation in a ROS-dependent manner. Histology and histopathology 4 39005145
2024 New insight into the CNC-bZIP member, NFE2L3, in human diseases. Frontiers in cell and developmental biology 4 39149514
2025 Novel roles of Nrf3-Trim5 axis in vascular smooth muscle cell dysfunctions and neointimal hyperplasia. Cardiovascular research 3 40377016
2024 Identification roles of NFE2L3 in digestive system cancers. Journal of cancer research and clinical oncology 3 38514488
2026 Emodin induces oxidative stress and Ferroptosis in hepatocellular carcinoma cells through the miR-4465/NFE2L3/HMGCR/GPX4 signaling axis. Life sciences 2 41534777
2025 The CNC-family transcription factor NRF3: A crucial therapeutic target for cancer treatment. Biochimica et biophysica acta. Molecular basis of disease 2 40081618
2025 NFE2L3 regulates inflammation and oxidative stress-related genes in the colon. Biochimica et biophysica acta. Molecular cell research 2 40360021
2023 Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway. Open life sciences 2 38027228
2022 NFE2L3 as a Novel Biomarker Associated With IL-2/STAT5/NLRP3 Signaling Pathway in Malignant Pleural Mesothelioma and Other Cancers. Frontiers in genetics 2 35664314
2026 BHLHE40 Is a Transcriptional Regulatory Target of NFE2L3 in Triple-Negative Breast Cancer. Oncology research 0 41613788
2026 A comprehensive review of the emerging role of NRF3 in ovarian cancer tumorigenesis and progression. Journal of ovarian research 0 41652483
2026 Nrf3: an emerging player in cancer, inflammation, and cellular homeostasis. Molecular biology reports 0 41838283
2026 6-O-Carboxypropyl-α-Tocotrienol Enhances the Anticancer Effects of Bortezomib Without Suppressing NRF1 and NRF3 in Colorectal Cancer Cells. Anticancer research 0 42049351
2026 LEF1/NFE2L3/TACC1 axis activates the AKT-mTOR pathway to promote the progression of esophageal squamous cell carcinoma. Journal of thoracic disease 0 42182760
2022 Nrf3 Functions Reversely as a Tumorigenic to an Antitumorigenic Transcription Factor in Obese Mice. The Tohoku journal of experimental medicine 0 36328531
2020 Correction to: Nrf3 promotes UV-induced keratinocyte apoptosis through suppression of cell adhesion. Cell death and differentiation 0 31641240

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