Affinage

NRF1

Nuclear respiratory factor 1 · UniProt Q16656

Length
503 aa
Mass
53.5 kDa
Annotated
2026-04-29
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NRF1 (also known as NFE2L1 or alpha-Pal/NRF-1) is a CNC-bZIP transcription factor that serves as a master regulator of proteasome homeostasis, antioxidant defense, and mitochondrial biogenesis, coordinating cellular proteostasis with metabolic adaptation. NRF1 is synthesized as an ER-resident glycoprotein anchored by its N-terminal domain; upon proteasome insufficiency it is retrotranslocated to the cytosol, proteolytically cleaved and activated by the aspartyl protease DDI2, deglycosylated by NGLY1, and translocated to the nucleus where it heterodimerizes with small Maf proteins to bind CNC-sMaf-binding elements (CsMBEs) and antioxidant response elements (AREs), driving expression of all 26S proteasome subunit genes, aggrephagy mediators (p62, GABARAPL1), ER homeostasis factors, and cholesterol-elimination genes (PMID:27528193, PMID:27528192, PMID:27676297, PMID:27723178, PMID:35129372, PMID:37658135, PMID:37060561). NRF1 activity is tuned by O-GlcNAcylation (OGT/HCF-1 complex), non-canonical oxyester-linked ubiquitination (SCF^FBS2–ARIH1), SIAH2-mediated degradation at K230, ATM-dependent phosphorylation promoting nuclear entry under oxidative stress, TBK1 phosphorylation at Ser318 inactivating the NRF1–TFAM axis during viral infection, and HDAC3-mediated deacetylation at K105/K139 (PMID:29941490, PMID:39116872, PMID:30833558, PMID:30642892, PMID:37409632, PMID:39198723). Beyond proteostasis, NRF1 cooperates with PGC-1α/β and ERRα to activate nuclear-encoded mitochondrial genes (TFAM, cytochrome c, FDXR, FUNDC1), is essential for hepatocyte survival and lipid homeostasis, drives spermatogenesis and cardiac regeneration programs, and recruits ncPRC1.3 for neuronal developmental gene activation (PMID:33554448, PMID:26492917, PMID:20561910, PMID:12808106, PMID:25092871, PMID:28754714, PMID:34489413, PMID:34637754).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2000 Medium

    Establishing NRF1 as a methylation-sensitive transcription factor at specific promoters resolved how CpG methylation could silence NRF1-dependent genes such as FMR1 in brain and testis.

    Evidence EMSA/supershift assays with brain/testis extracts showing NRF1 binding abolished by methylation, plus reporter mutagenesis

    PMID:11058604

    Open questions at the time
    • No genome-wide survey of methylation-NRF1 interplay at this stage
    • Functional consequence of NRF1 loss at FMR1 not shown in vivo
  2. 2003 High

    Demonstration that Nrf1 is essential for hepatocyte viability and antioxidant defense — and that Nrf1/Nrf2 double knockouts die embryonically with massive oxidative damage — established NRF1 as a non-redundant component of the cellular antioxidant transcription network.

    Evidence Chimeric mouse analysis for Nrf1, double-KO embryos for Nrf1/Nrf2, ROS measurements and antioxidant gene profiling

    PMID:12808106 PMID:12968018

    Open questions at the time
    • Specific antioxidant target genes directly bound by NRF1 not yet identified
    • Relative contribution of NRF1 vs NRF2 to individual ARE targets unclear
  3. 2005 High

    Discovery that NRF1/NRF2 regulate GCLC transcription indirectly via AP-1 and NF-κB family members, and that NRF1 promotes neurite outgrowth via IAP/CD47, expanded the functional repertoire beyond simple ARE binding to include indirect transcriptional cascades and neuronal differentiation.

    Evidence Null fibroblast rescue with mutant reporters (GCLC); dominant-negative NRF1 in neuroblastoma and primary neurons (neurite outgrowth)

    PMID:15988009 PMID:15992771

    Open questions at the time
    • Mechanism by which NRF1 controls AP-1/NF-κB expression not delineated
    • Neurite outgrowth pathway downstream of IAP/CD47 not mapped
  4. 2006 High

    Identification of the N-terminal domain (aa 1–124) as an ER-targeting signal that negatively regulates NRF1 transcriptional activity resolved why NRF1 is inactive under basal conditions and distinguished its regulation from Keap1-dependent NRF2 control.

    Evidence Immunocytochemistry with ER markers, deletion/domain-swap mutagenesis in WT and mutant MEFs

    PMID:16872277

    Open questions at the time
    • Retrotranslocation mechanism not yet identified
    • Identity of protease releasing NRF1 from ER unknown
  5. 2011 Medium

    Showing that proteasome inhibition stabilizes full-length Nrf1 yet paradoxically reduces its transactivation activity supported a model in which the proteasome itself participates in NRF1 processing by removing the inhibitory N-terminal domain.

    Evidence Proteasome inhibitor treatment, ubiquitination assays, EpRE-reporter kinetics

    PMID:22216197

    Open questions at the time
    • Exact cleavage site and responsible protease not identified
    • Single-lab observation without in vivo validation
  6. 2014 High

    Liver-specific Nrf1 knockout revealed NRF1 as a direct suppressor of lipid accumulation and the cystine/glutamate antiporter xCT, establishing its role in hepatic lipid homeostasis beyond antioxidant defense.

    Evidence Inducible liver-specific Nrf1 KO mouse, lipid profiling, ARE-reporter and promoter occupancy studies

    PMID:25092871

    Open questions at the time
    • How NRF1 and NRF2 switch at the xCT ARE under stress not mechanistically defined
    • Downstream lipotoxic mediators not identified
  7. 2015 High

    Multiple studies converged to show that NRF1 links proteasome gene expression to mTORC1 signaling, cooperates with PGC-1α/EglN2 on mitochondrial gene promoters, and is required for β-cell glucose sensing — establishing NRF1 as a metabolic integrator across tissues.

    Evidence TSC-KO/rapamycin for mTORC1–NRF1 axis; ChIP-seq for EglN2–PGC-1α–NRF1 at FDXR; β-cell-specific Nrf1 cKO with insulin secretion assays

    PMID:25556857 PMID:26017155 PMID:26492917

    Open questions at the time
    • Direct phosphorylation or signal transduction from mTORC1 to NRF1 protein not identified
    • Whether NRF1 mitochondrial targets differ across tissues unknown
  8. 2015 High

    Genome-wide DNase-seq in methylation-deficient cells proved that DNA methylation directly competes with NRF1 binding at thousands of sites, establishing a general epigenetic gating mechanism for NRF1 target selection.

    Evidence DNase-I mapping in murine ES cells ± DNA methyltransferases, motif deletion experiments

    PMID:26675734

    Open questions at the time
    • Whether NRF1 actively protects bound sites from remethylation not fully resolved
    • Tissue-specific methylation patterns and NRF1 access not examined
  9. 2016 High

    Identification of DDI2 as the aspartyl protease required for NRF1 cleavage and activation — conserved from C. elegans to mammals — resolved the long-standing question of how NRF1 is proteolytically activated during the proteasome 'bounce-back' response.

    Evidence DDI2 KO cells with protease-dead rescue (mammalian); genetic screen and epistasis in C. elegans SKN-1A pathway

    PMID:27528192 PMID:27528193

    Open questions at the time
    • Precise DDI2 cleavage site on NRF1 not mapped
    • Signals triggering DDI2 activation not identified
  10. 2016 Medium

    Demonstration that NRF1 can be retrotranslocated and cleaved even under complete proteasome blockade revealed a proteasome-independent processing route, refining the earlier model that the proteasome itself was the activating protease.

    Evidence Complete active-site proteasome inhibition with subcellular fractionation and western blot for NRF1 isoforms

    PMID:27676297

    Open questions at the time
    • Identity of proteasome-independent processing enzyme (later shown to be DDI2) not confirmed in this study
    • Single-lab biochemical observation
  11. 2016 High

    Genetic evidence that small Maf triple-KO phenocopies Nrf1 liver-KO (steatosis, proteasomal gene dysregulation) proved that sMaf proteins are obligate heterodimeric partners for NRF1 function in vivo.

    Evidence Liver-specific conditional sMaf triple-KO mice with gene expression and phenotypic comparison to Nrf1 KO

    PMID:27723178

    Open questions at the time
    • Relative contribution of individual sMaf isoforms not resolved
    • Whether sMaf availability limits NRF1 activity in non-hepatic tissues unknown
  12. 2018 High

    OGT/HCF-1-mediated O-GlcNAcylation was established as a major post-translational modifier of NRF1 stability and transcriptional output, with therapeutic implications for cancer proteasome inhibitor sensitivity.

    Evidence Reciprocal Co-IP/MS, OGT inhibition in vitro and xenograft models; replicated across three independent studies

    PMID:26231763 PMID:28625484 PMID:29941490

    Open questions at the time
    • Contradictory conclusions on whether O-GlcNAcylation stabilizes or destabilizes NRF1 across studies
    • Specific O-GlcNAc sites beyond PEST2 domain not fully catalogued
  13. 2018 High

    Brown-adipocyte-specific Nrf1 deletion showed that NRF1-driven proteasome upregulation is essential for ER homeostasis during cold-induced thermogenesis, linking NRF1 to adaptive tissue remodeling.

    Evidence BAT-specific cKO mouse, cold exposure, proteasome activity and ER stress markers

    PMID:29400713

    Open questions at the time
    • Whether NRF1 targets in BAT extend beyond proteasome subunits not fully catalogued
    • Upstream signal from cold to NRF1 activation not identified
  14. 2018 High

    NGLY1 deficiency was shown to impair NRF1-dependent mitophagy and trigger innate immune activation via cGAS-STING and MDA5-MAVS, connecting NRF1 deglycosylation to mitochondrial quality control and inflammation.

    Evidence NGLY1 KO in human and mouse cells, mitophagy assays, innate immune pathway measurements, NRF2 pharmacological rescue

    PMID:30135079

    Open questions at the time
    • Whether NRF1 glycosylation state directly controls specific mitophagy gene promoters not shown
    • Contribution of NRF1 vs other NGLY1 substrates not fully deconvolved
  15. 2019 High

    ATM phosphorylation of NRF1 specifically in response to oxidative stress (not DNA damage) drives NRF1 dimerization and nuclear entry to upregulate mitochondrial genes, establishing a kinase-level switch linking ROS sensing to mitochondrial biogenesis.

    Evidence ATM activation assays distinguishing stimuli, phosphorylation assays, ATM-null cell mitochondrial function

    PMID:30642892

    Open questions at the time
    • Specific NRF1 phosphorylation sites by ATM not mapped
    • Whether other oxidative-stress kinases also target NRF1 unknown
  16. 2019 High

    SIAH2-mediated ubiquitination at K230 degrades NRF1 under hypoxia, suppressing nuclear-encoded mitochondrial genes and promoting the Warburg effect — identifying a specific E3 ligase and degron for NRF1 turnover in cancer metabolism.

    Evidence Ubiquitination assays, K230 mutagenesis, hypoxia experiments, gene expression profiling

    PMID:30833558

    Open questions at the time
    • Whether SIAH2 targets all NRF1 isoforms equally unknown
    • Relationship to p97/ERAD-mediated NRF1 degradation pathway not clarified
  17. 2019 High

    High-resolution ChIP-exo revealed that NRF1 and NRF2 have overlapping but distinct genomic preferences (AT-rich vs GC-rich ARE flanks), explaining differential target gene selection and isoform-specific transcriptional programs.

    Evidence ChIP-exo sequencing with RNA-seq in U2OS cells, motif analysis

    PMID:31628195

    Open questions at the time
    • Whether flanking-sequence preference varies across cell types not tested
    • Structural basis for differential motif recognition not determined
  18. 2021 High

    NRF1 was found to be an integral component of ncPRC1.3 in neurons, required for AUTS2-Polycomb-mediated transcriptional activation and motor neuron differentiation — a function entirely distinct from its known proteostasis/metabolic roles.

    Evidence AUTS2 HX domain mutation, Co-IP, ChIP, motor neuron differentiation from mouse ESCs

    PMID:34637754

    Open questions at the time
    • Whether NRF1-PRC1.3 interaction occurs in non-neuronal contexts unknown
    • Structural basis of NRF1 incorporation into PRC1.3 not determined
  19. 2021 High

    NRF1 was shown to couple mitochondrial biogenesis with mitophagy by transcriptionally activating FUNDC1 via PGC-1α, and to be essential for neonatal cardiac regeneration through dual proteasome and redox gene activation.

    Evidence ChIP on Fundc1 promoter plus BAT-specific Fundc1 cKO (mitophagy); cardiac-specific Nrf1 deletion plus overexpression in I/R model

    PMID:33554448 PMID:34489413

    Open questions at the time
    • Full repertoire of NRF1 mitophagy targets beyond FUNDC1 not defined
    • Whether NRF1's cardiac role requires DDI2-mediated activation not tested
  20. 2022 High

    Genome-wide characterization of the Nrf1-MafG heterodimer binding (CsMBEs) revealed that proteasome subunit genes are part of a broader proteostasis transcriptional network (ERAD, chaperones, ubiquitin pathway), with SINE B2 transposable elements contributing binding site diversity.

    Evidence Tethered Nrf1-MafG in sMaf triple-KO fibroblasts, ChIP-seq, RNA-seq

    PMID:35129372

    Open questions at the time
    • Whether SINE B2-derived CsMBEs are functional in all tissues not assessed
    • Chromatin accessibility requirements for CsMBE activity not examined
  21. 2023 High

    NRF1 was shown to directly induce aggrephagy genes (p62, GABARAPL1) during proteasome dysfunction, expanding the bounce-back response beyond proteasome subunit transcription to include selective autophagy — and NRF1/NRF2 co-regulation of cholesterol elimination genes was revealed by double-KO hepatocytes.

    Evidence RNA-seq and ChIP for NRF1 on p62/GABARAPL1 promoters; hepatocyte-specific NRF1/NRF2 double-KO with ChIP-seq and cholesterol challenge

    PMID:37060561 PMID:37658135

    Open questions at the time
    • Relative contribution of aggrephagy vs proteasome upregulation to cellular survival not quantified
    • Mechanism of NRF1/NRF2 cooperativity at cholesterol gene promoters not defined
  22. 2023 High

    TBK1 phosphorylation of NRF1 at Ser318 during viral infection inactivates the NRF1-TFAM axis, suppressing mtDNA release and attenuating innate antiviral responses — identifying NRF1 as a pathogen-targeted node linking mitochondrial integrity to immunity.

    Evidence Kinase assay, Ser318 mutagenesis, knock-in mouse model, mtDNA release and innate immune measurements

    PMID:37409632

    Open questions at the time
    • Whether other viruses exploit TBK1-NRF1 axis not tested
    • Interplay between TBK1 and ATM phosphorylation of NRF1 not examined
  23. 2024 High

    Discovery that SCF^FBS2 and ARIH1 cooperate to attach non-canonical oxyester-linked ubiquitin chains to NRF1's N-GlcNAc residues — inhibiting DDI2-mediated activation — revealed an unexpected glycan-dependent ubiquitin code controlling the bounce-back response.

    Evidence In vitro reconstitution on glycopeptides, cell-based ubiquitination, mass spectrometry, mutagenesis

    PMID:39116872

    Open questions at the time
    • Physiological contexts in which oxyester ubiquitination dominates over canonical degradation unknown
    • Whether ENGASE-generated N-GlcNAc is the sole trigger for this pathway not confirmed
  24. 2024 Medium

    HDAC3-mediated deacetylation of NRF1 at K105/K139 was shown to reduce nuclear NRF1 stability and promote NRF1-p65 interaction driving neuroinflammation, identifying acetylation as yet another post-translational layer of NRF1 regulation.

    Evidence K105R/K139R mutagenesis, Co-IP, dual-luciferase reporter, MCAO/R mouse stroke model

    PMID:39198723

    Open questions at the time
    • Single-lab study; independent replication needed
    • Whether acetylation and O-GlcNAcylation compete at overlapping sites not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive characterization of NRF1 activation, the precise DDI2 cleavage site on NRF1, the structural basis for NRF1-sMaf DNA recognition at CsMBEs versus AREs, the integration logic among competing post-translational modifications (O-GlcNAcylation, oxyester ubiquitination, phosphorylation, acetylation), and whether NRF1's PRC1.3-associated role extends beyond neurons remain unresolved.
  • DDI2 cleavage site on NRF1 not mapped
  • No structural model of NRF1-sMaf-DNA complex
  • Integration of competing PTMs not systematically analyzed
  • Tissue scope of NRF1-PRC1.3 function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 12 GO:0003677 DNA binding 7
Localization
GO:0005634 nucleus 4 GO:0005783 endoplasmic reticulum 3 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-1852241 Organelle biogenesis and maintenance 7 R-HSA-392499 Metabolism of proteins 7 R-HSA-1430728 Metabolism 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9612973 Autophagy 3 R-HSA-4839726 Chromatin organization 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ARIH1AUTS2DDI2HCF1MAFGMCRS2OGTSIAH2
Complex memberships
NRF1-sMaf heterodimerOGT-HCF-1-NRF1 complexncPRC1.3

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Nrf1 is targeted to the endoplasmic reticulum via its N-terminal domain (NTD, amino acids 1-124), which negatively regulates its activity by anchoring it to the ER. Keap1 does not control Nrf1 activity or subcellular distribution, distinguishing Nrf1 regulation from Nrf2. Attachment of the NTD to Nrf2 redirected Nrf2 from the nucleus to the ER. Immunocytochemistry with ER marker co-localization, ectopic expression of wild-type and deletion mutants in wild-type and mutant MEFs, domain-swap experiments The Biochemical journal High 16872277
2016 The aspartyl protease DDI2 (DNA-damage inducible 1 homolog 2) is required to proteolytically cleave and activate Nrf1 in response to proteasome dysfunction. Deletion of DDI2 reduced the cleaved form of Nrf1 and impaired proteasome subunit upregulation; protease-dead DDI2 could not rescue these defects. DDI2 knockout cell lines, add-back of wild-type vs. protease-dead DDI2 mutant, western blot for Nrf1 cleavage forms, proteasome activity assays eLife High 27528192 27528193
2016 In C. elegans, ER-associated SKN-1A/Nrf1 is activated by the aspartic protease DDI-1, which cleaves it following proteasome dysfunction. Genes required for SKN-1A activation include regulators of ER traffic and a peptide N-glycanase, establishing a conserved ER-to-nucleus proteasome surveillance pathway. Comprehensive genetic screen (C. elegans), epistasis analysis, protease requirement assays eLife High 27528192
2015 mTORC1 activation promotes NRF1-dependent transcriptional upregulation of proteasome subunit genes, increasing cellular proteasome content. This was demonstrated through genetic activation of mTORC1 (TSC loss-of-function) as well as physiological stimuli (growth factors, feeding). Genetic loss-of-function (TSC knockout), pharmacological mTORC1 inhibition with rapamycin, NRF1 knockdown, proteasome content measurements Cell cycle (Georgetown, Tex.) Medium 26017155
2015 DNA methylation competes with NRF1 binding in vivo; NRF1 occupies thousands of additional sites in unmethylated genomes. Restoring de novo methyltransferase activity initiates remethylation at NRF1-bound sites and outcompetes NRF1 binding. Removal of neighboring motifs in cis or a cooperating TF in trans causes local hypermethylation and loss of NRF1 binding. DNase-I hypersensitive site mapping in murine stem cells with/without DNA methylation, genetic manipulation of methyltransferases, motif deletion experiments Nature High 26675734
2018 O-GlcNAc transferase (OGT) and host cell factor C1 (HCF-1) form a complex with NRF1; O-GlcNAcylation catalyzed by OGT stabilizes NRF1 and is essential for NRF1-mediated upregulation of proteasome subunit genes. OGT inhibition sensitized cancer cells to proteasome inhibitors in vitro and in xenograft models. Immunoprecipitation and mass spectrometry, OGT inhibition, xenograft mouse model, meta-analysis of cancer proteomics data Molecular and cellular biology High 29941490
2017 Nrf1 is negatively regulated by O-GlcNAcylation via OGT interaction through HCF-1; O-GlcNAcylation decreases Nrf1 protein stability and transactivation activity by promoting ubiquitination. The PEST2 degron within Nrf1 is identified as the O-GlcNAcylation site. Co-immunoprecipitation, OGT overexpression, proteasomal inhibition, ubiquitination assays, domain mapping Free radical biology & medicine Medium 28625484
2015 Nrf1 O-GlcNAcylation by OGT negatively regulates Nrf1/TCF11 protein stability and transactivation activity, promoting ubiquitination and turnover. This effect is glucose-concentration dependent. OGT interaction identified by pulldown, co-immunoprecipitation, ubiquitination assays, reporter assays FEBS letters Medium 26231763
2016 Under conditions of complete proteasome blockade, Nrf1 (p120) can still be retrotranslocated into the cytosol and proteolytically cleaved to the active p110 form in a proteasome-independent manner, indicating a proteasome-independent processing pathway exists. Complete proteasome active-site inhibition, subcellular fractionation, western blot for Nrf1 processing forms, transcription reporter assays Current biology : CB Medium 27676297
2024 SCFFBS2 (an N-glycan-recognizing E3 ligase) cooperates with the RBR-type E3 ligase ARIH1 to ubiquitinate Nrf1 through oxyester bonds (non-canonical ubiquitination) at N-GlcNAc residues generated by ENGASE. This atypical ubiquitin chain assembly requires UBE2L3 and inhibits DDI2-mediated Nrf1 activation. In vitro reconstitution of polyubiquitination on glycopeptides, cell-based ubiquitination assays, mass spectrometry, mutagenesis Molecular cell High 39116872
2019 SIAH2, a hypoxia-activated E3 ubiquitin ligase, degrades NRF1 through ubiquitination on lysine 230, reducing nuclear-encoded mitochondrial gene expression including pyruvate dehydrogenase beta, promoting the Warburg effect and metabolic reprogramming. Ubiquitination assays, site-directed mutagenesis (K230), hypoxia experiments, gene expression profiling, tumor microenvironment analysis Nature communications High 30833558
2019 ATM, when activated by oxidative stress (but not by DNA damage), phosphorylates NRF1, leading to NRF1 dimerization, nuclear translocation, and upregulation of nuclear-encoded mitochondrial genes to enhance electron transport chain capacity and restore mitochondrial function. ATM activation assays distinguishing oxidative vs. DNA damage stimuli, phosphorylation assays, subcellular fractionation, mitochondrial function assays in ATM-null cells The Journal of cell biology High 30642892
2021 PGC-1α and NRF1 transcriptionally upregulate FUNDC1 (a mitophagy receptor) by NRF1 binding to the consensus site in the Fundc1 promoter, coupling mitochondrial biogenesis with mitophagy. Specific knockout of Fundc1 in BAT impaired mitochondrial turnover and adaptive thermogenesis. ChIP demonstrating NRF1 binding to Fundc1 promoter, conditional knockout mouse, mitochondrial function assays, thermogenesis phenotyping EMBO reports High 33554448
2018 Cold adaptation induces Nrf1 in brown adipose tissue (BAT) to increase proteasomal activity, which is crucial for maintaining ER homeostasis during thermogenic activity. Brown-adipocyte-specific deletion of Nrf1 caused ER stress, tissue inflammation, diminished mitochondrial function, and BAT whitening under thermogenic conditions. Tissue-specific conditional knockout mouse, cold exposure experiments, proteasome activity assays, ER stress markers, mitochondrial function measurements Nature medicine High 29400713
2018 NGLY1 regulates mitochondrial homeostasis through NRF1; NGLY1-deficient cells show impaired mitophagy and fragmented mitochondria with cGAS-STING and MDA5-MAVS pathway activation. Pharmacological activation of NRF2 (a non-glycosylated homolog) restores mitochondrial homeostasis in NGLY1-deficient cells. NGLY1 knockout human and mouse cells, mitophagy assays, innate immune pathway activation measurements, NRF1 functional rescue experiments The Journal of experimental medicine High 30135079
2003 Nrf1 is essential for hepatocyte survival during development; Nrf1-deficient cells contributed to fetal but not adult liver. Loss of Nrf1 caused liver cell apoptosis, increased oxidative stress, impaired antioxidant gene expression, and sensitized cells to TNF-mediated cytotoxicity. Chimeric mouse analysis, primary hepatocyte culture, oxidative stress measurements, antioxidant gene expression assays Molecular and cellular biology High 12808106
2003 Nrf1 and Nrf2 have overlapping functions in antioxidant gene expression during early development; compound Nrf1/Nrf2 double-knockout mice die at E9-10 with extensive apoptosis and severely impaired antioxidant defense gene expression compared with single knockouts. Cell death was mediated by ROS activation of p53/Noxa. Double-knockout mouse generation, reactive oxygen species measurement, antioxidant gene expression, rescue by reduced oxygen or antioxidants, p53/Noxa induction assays The Journal of biological chemistry High 12968018
2005 Nrf1 and Nrf2 regulate rat GCLC transcription indirectly by modulating the expression of key AP-1 (c-Jun, c-Fos) and NF-κB (p50, p65) family members. Overexpression of Nrf1 or Nrf2 restored GCLC promoter activity but not if AP-1 and NF-κB binding sites were mutated. Nrf1/Nrf2 null fibroblasts, reporter gene assays with site-directed mutagenesis, mRNA/protein expression analysis, nuclear binding activity assays Molecular and cellular biology High 15988009
2014 Liver-specific Nrf1 knockout causes lipid accumulation in hepatocytes with altered fatty acid composition due to upregulation of FA metabolism genes. Nrf1 normally suppresses the cystine/glutamate antiporter xCT by occupying an ARE in its promoter; upon severe oxidative stress, Nrf1 is displaced and Nrf2 is recruited. Inducible liver-specific Nrf1 knockout mouse, lipid analysis, gene expression profiling, ARE reporter assays Molecular and cellular biology High 25092871
2016 Small Maf (sMaf) proteins are indispensable heterodimeric partners for Nrf1 in the liver; liver-specific sMaf triple-deficient mice recapitulate the Nrf1 liver-specific KO phenotype (hepatic steatosis, dysregulation of metabolic and proteasomal genes), providing genetic evidence that sMaf proteins mediate Nrf1 function. Liver-specific conditional sMaf triple-knockout mice, gene expression profiling, phenotypic comparison with Nrf1 KO Genes to cells : devoted to molecular & cellular mechanisms High 27723178
2022 The Nrf1-MafG heterodimer binds CNC-sMaf-binding elements (CsMBEs) to activate proteasome subunit genes and broader proteostasis-related genes (ER-associated degradation, chaperone, ubiquitin-mediated degradation pathways). SINE B2 transposable elements harbor CsMBEs and contribute to target gene diversity. Tethered Nrf1-MafG heterodimer in small Maf triple-knockout fibroblasts, ChIP-seq, RNA-seq Molecular and cellular biology High 35129372
2021 NRF1 has an integral role in ncPRC1.3 (non-canonical Polycomb repressive complex 1.3) recruitment to chromatin in neurons, being required for AUTS2-Polycomb-mediated transcriptional activation of developmental genes. NRF1 is necessary for motor neuron differentiation from mouse embryonic stem cells in this context. AUTS2 HX domain mutation analysis, Co-IP, ChIP, motor neuron differentiation assays from mouse ESCs Molecular cell High 34637754
2015 EglN2/PHD1 forms an activator complex with PGC1α and NRF1 on chromatin to promote transcription of ferridoxin reductase (FDXR) and maintain mitochondrial function in breast cancer cells. NRF1 motif enrichment was identified in EglN2-activated genes by integrative genomic analyses. ChIP-seq, gene expression profiling, NRF1 motif enrichment analysis, EglN2 depletion, mitochondrial respiration assays The EMBO journal High 26492917
2020 ATF4 represses NRF1 transcriptional activity by binding to the NRF1 promoter region, thereby downregulating TFAM expression and causing mitochondrial dysfunction in alcoholic liver disease. Hepatocyte-specific ATF4 knockout mice, TFAM overexpression mice, ChIP demonstrating ATF4 binding to NRF1 promoter, gene expression analysis, mitochondrial function assays Gut High 33177163
2023 Virus-activated kinase TBK1 phosphorylates NRF1 at Ser318, triggering inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in strategy mimicking TBK1-NRF1 signaling showed that interrupting this connection ablated mtDNA release and attenuated innate antiviral response. TBK1 kinase assay, site-directed mutagenesis (Ser318), knock-in mouse model, innate immune activation assays, mtDNA release measurement The EMBO journal High 37409632
2019 NRF1 coordinates with DNA methylation to regulate spermatogenesis; conditional NRF1 ablation in gonocytes dramatically downregulated germline genes including Asz1, blocked germ cell proliferation, and caused male infertility in mice. NRF1 binds directly to promoters of germline-specific genes. Conditional knockout mouse, ChIP, gene expression analysis, fertility phenotyping FASEB journal High 28754714
2015 Nrf1 is a transcriptional activator of Herpud1 (an ER homeostasis protein) through antioxidant response elements in the Herpud1 promoter; Nrf1 knockout cells show decreased Herpud1 expression and inability to induce Herpud1 in response to ER stress. Nrf1 knockout cells, transactivation reporter assays, chromatin immunoprecipitation, ER stress induction FEBS letters High 25637874
2009 MCRS2 physically interacts with Nrf1 through the CNC-bZIP domain of Nrf1 (residues 354-447) and represses Nrf1-mediated transcriptional activation. MCRS2 colocalizes with Nrf1 in the nucleus without altering Nrf1 redistribution. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, immunofluorescence, reporter gene assays BMC cell biology Medium 19187526
2011 Nrf1 is ubiquitinated and degraded by the 26S proteasome; proteasomal inhibition stabilizes full-length Nrf1 but paradoxically inhibits its transactivation activity, supporting the model that the proteasome processes Nrf1 into its active form by removing its inhibitory N-terminal ER-anchoring domain. Hypoxia activates Nrf1 reporter activity. Proteasomal inhibitor treatment, immunoprecipitation for ubiquitination, EpRE-luciferase reporter assays, half-life determination, hypoxia experiments PloS one Medium 22216197
2014 Nrf1 physically interacts with androgen receptor (AR) and enhances AR DNA-binding activity; siRNA-mediated Nrf1 silencing attenuated AR transactivation while p65-Nrf1 overexpression enhanced it. Nrf2 suppresses AR transactivation by stimulating nuclear accumulation of p120-Nrf1. siRNA knockdown, Nrf1 overexpression, AR transactivation reporter assays, nuclear fractionation, Co-IP for Nrf1-AR interaction PloS one Medium 24466341
2019 NRF1 transcriptionally activates StAR (steroidogenic acute regulatory protein) by directly binding to two NRF1-binding sites on the mouse Star promoter at positions -1445/-1422 and -44/-19, positively regulating testosterone synthesis. Dual-luciferase reporter assays, ChIP, EMSA supershift assays, site-directed mutagenesis of NRF1 binding sites, NRF1 overexpression/knockdown The Journal of steroid biochemistry and molecular biology High 31028793
2017 HBZ (HTLV-1 bZIP factor) physically interacts with NRF-1 and inhibits NRF-1 DNA-binding ability, thereby suppressing TDP1 gene expression; NRF-1 is identified as a direct positive transcriptional regulator of TDP1 through a conserved NRF-1 binding site in the TDP1 core promoter. Co-immunoprecipitation (HBZ-NRF1), dominant-negative NRF1, NRF1 overexpression/shRNA, TDP1 promoter reporter assays, NRF1 binding site identification Scientific reports Medium 28993637
2018 LSD1-ERRα-mediated transcriptional activation at target gene TSSs requires NRF1 as an essential promoter-tethering factor for LSD1 recruitment; NRF1 does not affect LSD1 enzymatic activity. All three factors (NRF1, LSD1, ERRα) are required for cell invasion in an MMP1-dependent manner via NRF1/LSD1/ERRα-mediated H3K9me2 demethylation. ChIP-seq, siRNA knockdown of each factor, invasion assays, histone modification analysis Scientific reports Medium 29968728
2023 NRF1 transcriptionally induces aggrephagy by directly targeting p62/SQSTM1 and GABARAPL1 genes in response to proteasome dysfunction, in addition to its known role inducing proteasome subunit genes. NRF1 is required for p62-positive puncta formation and colocalization with ULK1 and TBK1, and for phosphorylation of p62 at Ser403. Genome-wide transcriptome analysis (RNA-seq), ChIP for direct NRF1 binding, NRF1 knockdown, p62 phosphorylation assays, confocal microscopy for puncta formation Scientific reports High 37658135
2021 Nrf1 genetic deletion prevented neonatal cardiomyocytes from activating a transcriptional program required for heart regeneration after injury; conversely, Nrf1 overexpression protected the adult heart from ischemia/reperfusion injury. The protective function involves dual activation of the proteasome and redox balance. Neonatal heart regeneration model, Nrf1 cardiac-specific deletion, Nrf1 overexpression, I/R injury model, cardiomyocyte toxicity assays Nature communications High 34489413
2000 Alpha-Pal/NRF-1 binds the FMR1 promoter and its binding is abolished by DNA methylation; USF1, USF2, and alpha-Pal/NRF-1 are the major transcription factors binding the FMR1 promoter in brain and testis extracts, and NRF-1 binding site integrity is important for transcriptional activity in neuronal cells. EMSA/supershift assays with brain and testis extracts, methylation sensitivity assays, mutational analysis of promoter binding sites, reporter gene assays The Journal of biological chemistry Medium 11058604
2019 Distinct Nrf1 isoforms (Nrf1α, Nrf1β, Nrf1γ) differentially regulate ARE target genes; Nrf1α and Nrf1β dominantly upregulate >90% of differentially expressed genes while Nrf1γ acts as a dominant-negative inhibitor, counteracting Nrf1α/β activity on target genes including 26S proteasomal subunits. Tetracycline-inducible stable expression in Flp-In T-REx system, RNA-sequencing, quantitative RT-PCR validation Scientific reports Medium 30814566
2005 Alpha-Pal/NRF-1 induces neurite outgrowth in neuroblastoma cells and primary cortical neurons; a dominant-negative NRF-1 mutant inhibits neurite induction. This function is partly mediated through NRF-1's downstream target gene IAP/CD47. Stable and transient expression in IMR-32 cells, dominant-negative mutant, primary cortical neuron transfection, IAP antisense inhibition Biochemical and biophysical research communications Medium 15992771
2019 NRF1 and NRF2 have overlapping and distinct transcriptional targets; ChIP-exo sequencing revealed NRF2 prefers AREs flanked by GC-rich regions while NRF1 prefers AT-rich flanking regions, explaining their differential binding in specific cellular contexts. ChIP-exo sequencing combined with RNA-seq in U2OS cells, motif analysis The Journal of biological chemistry High 31628195
2019 NRF1 binds subtelomeric CpG island promoters and drives TERRA (telomeric repeat-containing RNA) expression when these sites are demethylated; targeted demethylation via CRISPR-dCas9-TET1 increased TERRA production in a NRF1-dependent manner. CRISPR-dCas9-TET1 epigenetic engineering for targeted demethylation, NRF1 binding assays, TERRA quantification International journal of molecular sciences Medium 31181625
2024 HDAC3 deacetylates NRF1, reducing its nuclear stability and promoting its interaction with p65/NF-κB. Pterostilbene inhibits HDAC3 activity, increasing NRF1 acetylation at K105 and K139, which inhibits NRF1-p65 interaction and reduces neuroinflammation. K105R and K139R Nrf1 mutants counteracted the protective effect. Dual-luciferase reporter, co-immunoprecipitation, site-directed mutagenesis (K105R, K139R), MCAO/R mouse model, OGD/R microglial model Cellular & molecular biology letters Medium 39198723
2023 NRF1 binds the METTL3 promoter to upregulate METTL3 transcription, which promotes m6A modification and IGF2BP2-dependent mRNA stability of GLRX, protecting against dopamine neuron degeneration in a Parkinson's disease mouse model. ChIP, dual luciferase reporter assays, RIP, MeRIP (m6A profiling), NRF1/METTL3 overexpression and KD in MPTP mouse model CNS neuroscience & therapeutics Medium 37735974
2015 Nrf1 deficiency in pancreatic β-cells causes impaired glucose-stimulated insulin secretion, elevated basal insulin release, and oxidative stress. Mechanistically, Nrf1 loss alters glucose metabolic enzyme expression (inducing hexokinase 1, suppressing glucokinase) and disrupts coupling of glycolysis to mitochondrial metabolism. Stable Nrf1 knockdown in MIN6 cells, β-cell-specific Nrf1 conditional KO mice, insulin secretion assays, glucose metabolism assays, gene expression analysis Antioxidants & redox signaling High 25556857
2010 PGC-1β directly interacts with NRF-1 and ERRα; deletion or mutation of NRF-1 and/or ERRα binding sites in target gene (cytochrome c, ATP synthase β, ALAS-1) promoters attenuates their activation by PGC-1β. Inhibition of NRF-1 by siRNA ablates PGC-1β-mediated mitochondrial biogenesis and oxidative phosphorylation. siRNA knockdown, promoter deletion/mutagenesis, co-expression studies, mitochondrial function assays Mitochondrion Medium 20561910
2023 NRF1 and NRF2 co-regulate genes that eliminate cholesterol and mitigate inflammation and oxidative damage in hepatocytes; combined NRF1/NRF2 deficiency (but not single deficiency) causes severe steatohepatitis, cholesterol overload, and altered bile acid metabolism. Therapeutic effects of NRF2-activating drug bardoxolone require NRF1. Hepatocyte-specific single and double KO mice, ChIP-seq for target gene identification, dietary cholesterol challenge, pharmacological bardoxolone treatment Cell reports High 37060561

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences of the United States of America 1610 12832613
2015 Competition between DNA methylation and transcription factors determines binding of NRF1. Nature 377 26675734
2003 Deficiency of the Nrf1 and Nrf2 transcription factors results in early embryonic lethality and severe oxidative stress. The Journal of biological chemistry 267 12968018
2005 Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Molecular and cellular biology 216 15988009
2016 Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1. eLife 194 27528192
2018 Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nature medicine 166 29400713
2016 The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction. eLife 150 27528193
2021 Mitophagy receptor FUNDC1 is regulated by PGC-1α/NRF1 to fine tune mitochondrial homeostasis. EMBO reports 131 33554448
2010 PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha. Mitochondrion 126 20561910
2003 Nrf1 is critical for redox balance and survival of liver cells during development. Molecular and cellular biology 125 12808106
2020 ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis. Gut 120 33177163
2018 N-glycanase NGLY1 regulates mitochondrial homeostasis and inflammation through NRF1. The Journal of experimental medicine 104 30135079
2006 Negative regulation of the Nrf1 transcription factor by its N-terminal domain is independent of Keap1: Nrf1, but not Nrf2, is targeted to the endoplasmic reticulum. The Biochemical journal 102 16872277
2021 Nrf1 promotes heart regeneration and repair by regulating proteostasis and redox balance. Nature communications 100 34489413
2003 ELAV inhibits 3'-end processing to promote neural splicing of ewg pre-mRNA. Genes & development 77 14522950
2000 Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome. The Journal of biological chemistry 77 11058604
2020 Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling. Cell death & disease 76 32732978
2015 mTORC1 signaling activates NRF1 to increase cellular proteasome levels. Cell cycle (Georgetown, Tex.) 76 26017155
2016 Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases. International journal of molecular sciences 73 27983596
2019 Endoplasmic reticulum-associated SKN-1A/Nrf1 mediates a cytoplasmic unfolded protein response and promotes longevity. eLife 71 30973820
2018 Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal development and homeostasis. Molecular neurodegeneration 71 30333037
2014 Transcription factor Nrf1 negatively regulates the cystine/glutamate transporter and lipid-metabolizing enzymes. Molecular and cellular biology 70 25092871
2015 EglN2 associates with the NRF1-PGC1α complex and controls mitochondrial function in breast cancer. The EMBO journal 69 26492917
2019 The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression. Nature communications 67 30833558
2019 Differential and overlapping targets of the transcriptional regulators NRF1, NRF2, and NRF3 in human cells. The Journal of biological chemistry 67 31628195
2017 The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo. Redox biology 66 28582729
2015 Changing gears in Nrf1 research, from mechanisms of regulation to its role in disease and prevention. Biochimica et biophysica acta 65 26254094
2016 A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy. Human molecular genetics 61 26962150
2019 ATM is activated by ATP depletion and modulates mitochondrial function through NRF1. The Journal of cell biology 60 30642892
2018 O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1. Molecular and cellular biology 59 29941490
2020 Defining the Functional Targets of Cap'n'collar Transcription Factors NRF1, NRF2, and NRF3. Antioxidants (Basel, Switzerland) 57 33096892
2015 CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion. Antioxidants & redox signaling 57 25556857
2014 Nrf1 and Nrf2 transcription factors regulate androgen receptor transactivation in prostate cancer cells. PloS one 57 24466341
2005 ELAV multimerizes on conserved AU4-6 motifs important for ewg splicing regulation. Molecular and cellular biology 56 16107705
2012 Defects of mtDNA replication impaired mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and chagasic patients: the role of Nrf1/2 and antioxidant response. Journal of the American Heart Association 50 23316324
2014 The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Experimental cell research 49 24462598
2023 Regulation and Functions of the ER-Associated Nrf1 Transcription Factor. Cold Spring Harbor perspectives in biology 46 35940907
2023 NRF1-mediated mitochondrial biogenesis antagonizes innate antiviral immunity. The EMBO journal 44 37409632
2022 LINC00839 promotes colorectal cancer progression by recruiting RUVBL1/Tip60 complexes to activate NRF1. EMBO reports 43 35876654
2021 NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain. Molecular cell 43 34637754
2018 Interplay between NRF1, E2F4 and MYC transcription factors regulating common target genes contributes to cancer development and progression. Cellular oncology (Dordrecht, Netherlands) 43 30047092
2021 Roles of CNC Transcription Factors NRF1 and NRF2 in Cancer. Cancers 42 33535386
2017 NRF1 coordinates with DNA methylation to regulate spermatogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 42 28754714
2015 Induction of Herpud1 expression by ER stress is regulated by Nrf1. FEBS letters 42 25637874
2018 Nrf1 is paved as a new strategic avenue to prevent and treat cancer, neurodegenerative and other diseases. Toxicology and applied pharmacology 41 30267745
2021 CLTRN, Regulated by NRF1/RAN/DLD Protein Complex, Enhances Radiation Sensitivity of Hepatocellular Carcinoma Cells Through Ferroptosis Pathway. International journal of radiation oncology, biology, physics 40 33508374
2022 NRF1-mediated microglial activation triggers high-altitude cerebral edema. Journal of molecular cell biology 38 35704676
2019 Long isoforms of NRF1 negatively regulate adipogenesis via suppression of PPARγ expression. Redox biology 38 31931283
2020 ER-Resident Transcription Factor Nrf1 Regulates Proteasome Expression and Beyond. International journal of molecular sciences 35 32456207
2018 Resistin destroys mitochondrial biogenesis by inhibiting the PGC-1α/ NRF1/TFAM signaling pathway. Biochemical and biophysical research communications 35 30172371
2018 Transcriptional regulation of the 26S proteasome by Nrf1. Proceedings of the Japan Academy. Series B, Physical and biological sciences 35 30305478
2015 Expression of Mitochondria-Associated Genes (PPARGC1A, NRF-1, BCL-2 and BAX) in Follicular Development and Atresia of Goat Ovaries. Reproduction in domestic animals = Zuchthygiene 35 25779891
2020 Disabling the Protease DDI2 Attenuates the Transcriptional Activity of NRF1 and Potentiates Proteasome Inhibitor Cytotoxicity. International journal of molecular sciences 33 31947743
2016 TCF11/Nrf1-Mediated Induction of Proteasome Expression Prevents Cytotoxicity by Rotenone. Antioxidants & redox signaling 33 27345029
2013 Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene. Journal of cell science 33 24198395
2010 The nrf1 and nrf2 balance in oxidative stress regulation and androgen signaling in prostate cancer cells. Cancers 32 24281119
2020 The PGC1α/NRF1-MPC1 axis suppresses tumor progression and enhances the sensitivity to sorafenib/doxorubicin treatment in hepatocellular carcinoma. Free radical biology & medicine 31 33276082
2020 Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma. Cancers 30 32344880
2020 Regulation of NRF1, a master transcription factor of proteasome genes: implications for cancer and neurodegeneration. Molecular biology of the cell 30 32924844
2017 Effects of NRF1 on steroidogenesis and apoptosis in goat luteinized granulosa cells. Reproduction (Cambridge, England) 30 28624767
2017 Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase. Free radical biology & medicine 30 28625484
2022 Long noncoding RNA LINC01132 enhances immunosuppression and therapy resistance via NRF1/DPP4 axis in hepatocellular carcinoma. Journal of experimental & clinical cancer research : CR 29 36071454
2016 Nrf1 can be processed and activated in a proteasome-independent manner. Current biology : CB 29 27676297
2005 A novel function of transcription factor alpha-Pal/NRF-1: increasing neurite outgrowth. Biochemical and biophysical research communications 29 15992771
2022 Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival. Blood advances 28 34649278
2015 Transcription factor Nrf1 is negatively regulated by its O-GlcNAcylation status. FEBS letters 28 26231763
2011 The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia. PloS one 28 22216197
2023 The transcription factor NRF1 (NFE2L1) activates aggrephagy by inducing p62 and GABARAPL1 after proteasome inhibition to maintain proteostasis. Scientific reports 27 37658135
2022 ACEA Attenuates Oxidative Stress by Promoting Mitophagy via CB1R/Nrf1/PINK1 Pathway after Subarachnoid Hemorrhage in Rats. Oxidative medicine and cellular longevity 27 35251464
2025 Neoleukin-2/15-armored CAR-NK cells sustain superior therapeutic efficacy in solid tumors via c-Myc/NRF1 activation. Signal transduction and targeted therapy 26 40025022
2024 Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation. Molecular cell 26 39116872
1999 Differential and inefficient splicing of a broadly expressed Drosophila erect wing transcript results in tissue-specific enrichment of the vital EWG protein isoform. Molecular and cellular biology 26 10330140
2020 NRF-1 and HIF-1α contribute to modulation of human VDAC1 gene promoter during starvation and hypoxia in HeLa cells. Biochimica et biophysica acta. Bioenergetics 24 32810507
2019 Distinct isoforms of Nrf1 diversely regulate different subsets of its cognate target genes. Scientific reports 24 30814566
2023 The N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis by disrupting NRF1 binding capacity. Cell reports 23 36989111
2015 Lack of aprataxin impairs mitochondrial functions via downregulation of the APE1/NRF1/NRF2 pathway. Human molecular genetics 23 25976310
2023 Complementary gene regulation by NRF1 and NRF2 protects against hepatic cholesterol overload. Cell reports 22 37060561
2023 NRF1 mitigates motor dysfunction and dopamine neuron degeneration in mice with Parkinson's disease by promoting GLRX m6 A methylation through upregulation of METTL3 transcription. CNS neuroscience & therapeutics 22 37735974
2022 Curcumin attenuates isoniazid-induced hepatotoxicity by upregulating the SIRT1/PGC-1α/NRF1 pathway. Journal of applied toxicology : JAT 22 35032049
2009 MCRS2 represses the transactivation activities of Nrf1. BMC cell biology 22 19187526
2022 Distinct Roles of Nrf1 and Nrf2 in Monitoring the Reductive Stress Response to Dithiothreitol (DTT). Antioxidants (Basel, Switzerland) 21 36009254
2024 Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 38901196
2022 Paeoniflorin Alleviates Skeletal Muscle Atrophy in Ovariectomized Mice through the ERα/NRF1 Mitochondrial Biogenesis Pathway. Pharmaceuticals (Basel, Switzerland) 20 35455387
2013 Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus. Journal of molecular endocrinology 20 23892277
2011 ELAV-mediated 3'-end processing of ewg transcripts is evolutionarily conserved despite sequence degeneration of the ELAV-binding site. Genetics 20 21705751
2016 Small Maf deficiency recapitulates the liver phenotypes of Nrf1- and Nrf2-deficient mice. Genes to cells : devoted to molecular & cellular mechanisms 19 27723178
2024 Potential effect of acupuncture on mitochondrial biogenesis, energy metabolism and oxidation stress in MCAO rat via PGC-1α/NRF1/TFAM pathway. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 18 38346661
2024 Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation. Cellular & molecular biology letters 18 39198723
2022 PGC-1α/NRF1-dependent cardiac mitochondrial biogenesis: A druggable pathway of calycosin against triptolide cardiotoxicity. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 17 36436616
2013 Novel genes FAM134C, C3orf10 and ENOX1 are regulated by NRF-1 and differentially regulate neurite outgrowth in neuroblastoma cells and hippocampal neurons. Gene 17 23939472
2010 Prolonged Nrf1 overexpression triggers adipocyte inflammation and insulin resistance. Journal of cellular biochemistry 17 21053274
2022 Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway. Frontiers in oncology 16 36591497
2021 The positive regulation loop between NRF1 and NONO-TFE3 fusion promotes phase separation and aggregation of NONO-TFE3 in NONO-TFE3 tRCC. International journal of biological macromolecules 16 33592266
2019 Transcription regulation of NRF1 on StAR reduces testosterone synthesis in hypoxemic murine. The Journal of steroid biochemistry and molecular biology 16 31028793
2019 Repression of TERRA Expression by Subtelomeric DNA Methylation Is Dependent on NRF1 Binding. International journal of molecular sciences 16 31181625
2022 Target Gene Diversity of the Nrf1-MafG Transcription Factor Revealed by a Tethered Heterodimer. Molecular and cellular biology 15 35129372
2020 Downregulation of miR‑486‑5p alleviates LPS‑induced inflammatory injury, oxidative stress and apoptosis in Chondrogenic cell ATDC5 by targeting NRF1. Molecular medicine reports 15 32705174
2019 T-2 toxin upregulates the expression of human cytochrome P450 1A1 (CYP1A1) by enhancing NRF1 and Sp1 interaction. Toxicology letters 15 31470059
2018 LSD1-ERRα complex requires NRF1 to positively regulate transcription and cell invasion. Scientific reports 15 29968728
2017 HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. Scientific reports 15 28993637