Affinage

NQO1

NAD(P)H dehydrogenase [quinone] 1 · UniProt P15559

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

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NQO1 is a FAD-dependent homodimeric oxidoreductase that functions as both a cytoprotective detoxification enzyme and a redox-sensitive scaffold regulating protein stability, mRNA translation, and NAD+ homeostasis. Its obligatory two-electron reduction of quinones, nitroaromatics, and azo dyes using NAD(P)H prevents one-electron redox cycling and ROS generation, while simultaneously regenerating NAD+ to fuel sirtuin and PARP activities (PMID:20361926, PMID:11154736, PMID:29706024). Beyond catalysis, NAD(P)H binding induces conformational changes that modulate NQO1's non-enzymatic functions: it binds and stabilizes intrinsically disordered proteins including p53, p73, SIRT6, HBx, and Tat against 20S proteasomal degradation, promotes translation of SERPINA1 mRNA through direct RNA binding, and co-localizes with Sirt2 on the mitotic spindle to supply NAD+ for microtubule deacetylation (PMID:28883796, PMID:27515817, PMID:29298345, PMID:32987030, PMID:31842909). NQO1 itself is regulated transcriptionally through the Keap1/Nrf2/ARE pathway and post-translationally by Akt-mediated phosphorylation at T128, which triggers Parkin-dependent ubiquitination and degradation; the common P187S polymorphism destabilizes FAD binding and accelerates NQO1 turnover, with pharmacogenomic consequences for idebenone bioactivation in Leber hereditary optic neuropathy (PMID:31358653, PMID:30518535, PMID:38272025).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Determining the genomic organization and transcriptional regulation of NQO1 established it as a dioxin-inducible gene with a defined six-exon structure, setting the framework for understanding its regulatory elements.

    Evidence Gene sequencing and nuclear run-on transcription assays in TCDD-treated HepG2 cells

    PMID:1657151

    Open questions at the time
    • Precise cis-regulatory elements (ARE/XRE) not yet mapped in this study
    • Protein-level regulation not addressed
  2. 2000 High

    Characterization of NQO1 as an obligate two-electron reductase that detoxifies quinones and generates antioxidant forms of ubiquinone/vitamin E established its dual role in xenobiotic metabolism and endogenous antioxidant defense, with transcriptional control via ARE and XRE elements.

    Evidence Enzyme activity assays, reporter gene assays, and genetic analysis

    PMID:11154736

    Open questions at the time
    • Non-enzymatic functions not yet recognized
    • Structural basis for obligate two-electron mechanism not resolved
  3. 2006 Medium

    NQO1-null mice revealed an unexpected role in adaptive immunity: loss of NQO1 caused NADH accumulation, impaired NF-κB activation, reduced B-cell numbers, and autoimmune susceptibility, extending NQO1 function beyond detoxification to immune homeostasis.

    Evidence NQO1-null mouse model with flow cytometry, immunoglobulin assays, and collagen-induced arthritis model

    PMID:16905546

    Open questions at the time
    • Whether immune phenotype is cell-autonomous vs. systemic NADH/NAD+ imbalance not resolved
    • Single lab observation
  4. 2010 High

    The discovery that NQO1 binds and stabilizes p53 against proteasomal degradation revealed a major non-enzymatic function—acting as a gatekeeper of ubiquitin-independent 20S proteasomal degradation of disordered proteins.

    Evidence Biochemical protein binding studies, KO/knockdown with oxidative stress readout

    PMID:20361926

    Open questions at the time
    • Structural basis of NQO1-p53 interaction unknown
    • Whether other IDPs are similarly stabilized not yet tested
  5. 2014 Medium

    Demonstrating that NQO1-mediated NAD+ regeneration restores SIRT1 activity and reduces PARP-1 hyperactivation established NQO1 as a critical NAD+ supplier linking redox metabolism to sirtuin/PARP signaling.

    Evidence β-Lapachone (NQO1 substrate) treatment with NAD+ measurement, SIRT1 activity and PARP-1 activation assays in cisplatin ototoxicity model

    PMID:24922076

    Open questions at the time
    • Pharmacological activation via β-lapachone; endogenous substrate flux not quantified
    • Single lab
  6. 2016 High

    Two advances resolved NQO1's structural pharmacology and an entirely new RNA-binding function: X-ray crystallography of an inhibitor-NQO1 complex defined the FAD-proximal binding interface and negative cooperativity between monomers, while RNP-IP and polysome profiling in KO mice showed NQO1 directly binds SERPINA1 mRNA and promotes its translation.

    Evidence X-ray crystallography of E6a-NQO1 complex; RNP immunoprecipitation, polysome profiling, and NQO1-KO mouse model

    PMID:26822308 PMID:27515817

    Open questions at the time
    • RNA-binding domain not mapped
    • Whether NQO1 regulates other mRNAs genome-wide not comprehensively tested
    • Negative cooperativity mechanism for endogenous substrates unresolved
  7. 2017 High

    Integrating the enzymatic, RNA-binding, and protein-stabilizing functions under a unifying model established NQO1 as a redox-dependent molecular switch whose conformation changes with the NAD(P)+/NAD(P)H ratio to toggle between catalytic and scaffolding modes.

    Evidence In vitro enzymatic assay, RNP immunoprecipitation, mRNA translation assay, structural analysis

    PMID:28883796

    Open questions at the time
    • Quantitative thresholds of NAD(P)H ratio that flip the switch not defined
    • In vivo confirmation of conformational switching limited
  8. 2018 Medium

    Co-localization of NQO1 with acetylated α-tubulin and Sirt2 on the mitotic spindle and midbody suggested a cell-division-specific NAD+ supply role, while transgenic NQO1-overexpressing mice showed enhanced NAD+/sirtuin activity mimicking caloric restriction with lifespan extension.

    Evidence Immunofluorescence co-localization with Sirt2 and acetyl-α-tubulin; transgenic mouse metabolomics and lifespan assay

    PMID:29298345 PMID:29706024

    Open questions at the time
    • NQO1-Sirt2 functional coupling not reconstituted biochemically
    • Spindle NAD+ supply not directly measured
    • CYB5R3 co-overexpressed in transgenic model complicates attribution
  9. 2019 High

    Identification of Akt phosphorylation at T128 triggering Parkin-mediated ubiquitination and degradation of NQO1 defined the first post-translational regulatory circuit for NQO1 turnover, with neuroprotective consequences validated in MPTP-treated mice; concurrently, structural studies confirmed ping-pong kinetics and showed the P187S polymorphism destabilizes FAD binding.

    Evidence In vitro kinase assay, mutagenesis (T128A), ubiquitination assay, MPTP mouse model; enzyme kinetics and FAD binding assays

    PMID:30518535 PMID:31358653

    Open questions at the time
    • Physiological signals upstream of Akt-NQO1 axis in neurons not defined
    • Whether other E3 ligases besides Parkin ubiquitinate NQO1 unknown
  10. 2019 Medium

    NQO1 was shown to stabilize SIRT6 against 26S proteasomal degradation, linking NQO1's protein-chaperone function to downstream AKT acetylation and XIAP stabilization in hepatocellular carcinoma, broadening the catalog of NQO1-stabilized IDPs.

    Evidence Co-immunoprecipitation, ubiquitination assay, NQO1 KO and SIRT6 rescue in orthotopic mouse tumor model

    PMID:31842909

    Open questions at the time
    • Whether NQO1-SIRT6 interaction is redox-regulated not tested
    • Single lab
  11. 2020 High

    Demonstrating that NQO1 stabilizes viral proteins HBx (HBV) and Tat (HIV-1) against 20S degradation extended the gatekeeper paradigm to viral pathogenesis, with NQO1 inhibition or knockdown blocking HBV cccDNA transcription and HIV-1 replication.

    Evidence Reciprocal Co-IP, NQO1 siRNA/dicoumarol treatment, cccDNA ChIP, HBV-infected humanized mouse model; Rev overexpression and Tat stability assays

    PMID:26059226 PMID:32987030

    Open questions at the time
    • Direct structural basis of NQO1-HBx/Tat binding not resolved
    • NQO1-Tat interaction less rigorously validated than NQO1-HBx
  12. 2024 High

    The first crystal structure of human NQO1 in complex with NADH revealed that cofactor binding decreases protein dynamics, stabilizes the dimer interface, and enables long-range structural cooperativity between active sites, providing the atomic basis for the molecular switch model; separately, clinical pharmacogenomics showed NQO1 polymorphisms determine idebenone efficacy in LHON by controlling its reduction state.

    Evidence Serial synchrotron crystallography with MD simulations; patient genotyping with idebenone reduction and respiratory function assays

    PMID:38272025 PMID:38501509

    Open questions at the time
    • Structures of NQO1 bound to protein or mRNA partners not yet determined
    • Full-length dynamics of NQO1 with NADPH (vs. NADH) not resolved
    • Prospective clinical validation of NQO1 genotyping for idebenone therapy needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis by which NQO1 recognizes diverse IDP clients and mRNA targets, the quantitative NAD(P)H thresholds that toggle enzymatic versus scaffolding modes in vivo, and whether the immune and metabolic phenotypes of NQO1 loss reflect cell-autonomous redox changes or systemic NAD+ depletion.
  • No structure of NQO1 bound to any protein client or mRNA
  • In vivo NAD+ flux through NQO1 not quantified in specific tissues
  • Genome-wide RNA target landscape not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 5 GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 3 GO:0016209 antioxidant activity 3 GO:0044183 protein folding chaperone 3
Localization
GO:0005829 cytosol 3 GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AKT1PPIAPRKNSERPINA1SIRT2SIRT6TP53TP73
Complex memberships
NQO1 homodimer

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 NQO1 is a FAD-dependent flavoprotein that catalyzes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes using NADH or NADPH as cofactors, thereby preventing redox cycling and depletion of intracellular thiol pools. NQO1 also binds to and stabilizes p53 against proteasomal degradation, suggesting a 'gatekeeping' role in regulating proteasomal degradation of specific proteins. Biochemical assays, review of in vitro reduction assays, protein binding studies, KO/knockdown with oxidative stress phenotypic readout Archives of biochemistry and biophysics High 20361926
2000 NQO1 is an obligate two-electron reductase that detoxifies quinones and can bioactivate certain antitumor quinones; it also generates antioxidant forms of ubiquinone and vitamin E as part of the plasma membrane redox system. Gene regulation occurs via the antioxidant response element (ARE) and xenobiotic response element (XRE) in the NQO1 promoter. Enzyme activity assays, reporter gene assays, genetic analysis Chemico-biological interactions High 11154736
1991 The human NQO1 gene spans ~20 kb with six exons and five introns. TCDD (dioxin) increases the rate of NQO1 transcription by ~3-fold, as shown by nuclear run-on experiments. The gene contains an Alu repetitive sequence and multiple polyadenylation signals in the sixth exon. Gene sequencing, primer extension analysis for transcription start site, nuclear run-on transcription assay in HepG2 cells treated with TCDD Biochemistry High 1657151
2017 NQO1 functions as an efficient intracellular generator of NAD+ for enzymes including PARP and sirtuins. NQO1 also acts as an mRNA-binding protein that controls translation of SERPINA1 (α-1-antitrypsin). Structural changes in NQO1 induced by the cellular NAD(P)+/NAD(P)H ratio modulate its ability to bind other proteins and mRNA, suggesting it acts as a redox-dependent molecular switch. In vitro enzymatic assay, RNP immunoprecipitation, mRNA translation assay, structural analysis Frontiers in physiology High 28883796
2019 Akt phosphorylates NQO1 at T128, triggering its polyubiquitination and proteasomal degradation, with Parkin acting as the E3 ubiquitin ligase. An unphosphorylatable NQO1 T128A mutant is more neuroprotective than wild-type NQO1, suppressing ROS and protecting against MPTP-induced dopaminergic cell death in mice. Co-immunoprecipitation, in vitro phosphorylation assay, site-directed mutagenesis (T128A), ubiquitination assay, in vivo MPTP mouse model with motor readout The Journal of neuroscience High 31358653
2016 NQO1 novel RNA-binding activity promotes SERPINA1 mRNA translation. NQO1 binds the 3'UTR and coding region of SERPINA1 mRNA (identified by RNP immunoprecipitation and microarray). NQO1 silencing decreased polysome loading on SERPINA1 mRNA and reduced A1AT protein levels; NQO1-KO mice showed reduced hepatic and serum A1AT and increased neutrophil elastase activity. RNP immunoprecipitation and microarray, biotin pulldown, polysome profiling, luciferase reporter assay, NQO1-KO mouse model Free radical biology & medicine High 27515817
2018 NAD(P)H binding induces a structural change in NQO1 that results in loss of immunoreactivity to antibodies targeting the C-terminal domain and helix 7 of the catalytic core. Under normal cellular conditions, NQO1 co-localizes with acetyl α-tubulin and the NAD+-dependent deacetylase Sirt2 on the centrosome, mitotic spindle, and midbody during cell division, suggesting NQO1 provides NAD+ for Sirt2-mediated microtubule deacetylation. Purified NQO1 conformational assay, immunoprecipitation after β-lapachone treatment, immunostaining co-localization with acetyl α-tubulin and Sirt2 PloS one Medium 29298345
2013 NQO1 mitochondrial targeting: NQO1 protein localizes not only to the cytosol but also to the endoplasmic reticulum (ER) and mitochondria. NQO1 and CYP1B1 targeting to mitochondrial or ER membranes is independent of CYP1A1 presence in those membranes. Subcellular fractionation of dioxin-treated wild-type and CYP1A1/CYP1B1/NQO1 knockout and knock-in mice Biochemical and biophysical research communications Medium 23692925
2019 NQO1 functions as a homodimer with two active sites formed from residues of both polypeptide chains. Catalysis proceeds via a substituted (ping-pong) enzyme mechanism involving the tightly bound FAD cofactor. The common polymorphic form p.P187S has markedly reduced FAD binding affinity, leading to lower stability and accelerated proteasomal degradation. Enzyme kinetics, structural analysis, FAD binding assays, stability measurements, mutagenesis Bioscience reports High 30518535
2016 Dicoumarol and related compounds bind to the NAD(P)H binding site of NQO1 and act as competitive inhibitors. Binding of dicoumarol generates negative cooperativity between the two NQO1 monomers, an effect abolished by mutation of Gly150 (but not Gly149 or Gly174). This negative cooperativity does not occur with NAD(P)H alone. Enzyme inhibition kinetics, site-directed mutagenesis (G150A, G149A, G174A), Gaussian network model analysis of protein dynamics BMC structural biology / Chembiochem Medium 26822308 31165578
2006 NQO1-null mice showed decreased B-cells, altered B cell homing, impaired primary and secondary immune responses, and susceptibility to autoimmune collagen-induced arthritis. Loss of NQO1 resulted in NADH accumulation, altered intracellular redox status, decreased NF-κB expression and activation, and altered chemokine/chemokine receptor expression. NQO1-null mouse model, flow cytometry, immunoglobulin assays, collagen-induced arthritis model, microarray, NF-κB activation assays The Journal of biological chemistry Medium 16905546
2020 Endogenous NQO1 binds to and protects the HBV X protein (HBx) from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment reduced HBx recruitment to cccDNA and inhibited cccDNA transcriptional activity, establishing that NQO1-mediated stabilization of HBx is required for HBV replication. Co-immunoprecipitation (NQO1-HBx interaction), NQO1 siRNA knockdown, dicoumarol inhibition, cccDNA ChIP assay, HBV-infected cell and humanized mouse model Journal of hepatology High 32987030
2015 HIV-1 Rev downregulates Tat expression by reducing endogenous NQO1 levels. NQO1 stabilizes HIV-1 Tat protein against degradation (dicoumarol treatment destabilizes Tat); Rev-mediated reduction of NQO1 promotes Tat degradation, thereby inhibiting HIV-1 replication. Western blot, Rev expression constructs, dicoumarol (NQO1 inhibitor) treatment, ubiquitination assays, co-immunoprecipitation Nature communications Medium 26059226
2019 NQO1 activates AMPK in an OGD-dependent manner via the CD38/cADPR/RyR/Ca2+/CaMKII signaling cascade, suppressing mTOR/S6K/4E-BP1 signaling and promoting cancer cell death. NQO1 depletion prevents AMPK-induced cancer cell death under OGD. siRNA knockdown of NQO1, Ca2+/CaMKII inhibitors, RyR and CD38 siRNA knockdown, AMPK phosphorylation assays Scientific reports Medium 25586669
2019 NQO1 protects SIRT6 from ubiquitin-mediated 26S proteasomal degradation by direct binding. Stabilized SIRT6 reduces AKT acetylation, increasing AKT phosphorylation and activity, which then phosphorylates XIAP at Ser87, stabilizing it and promoting apoptosis evasion in hepatocellular carcinoma. Co-immunoprecipitation (NQO1-SIRT6 interaction), ubiquitination assay, NQO1 knockout and SIRT6 rescue experiments, orthotopic mouse tumor model Cell communication and signaling Medium 31842909
2022 NQO1 binds to PPIA (peptidyl-prolyl cis-trans isomerase A) and prevents its oxidation at cysteine C161, stabilizing it. Stabilized PPIA activates CD147 on cell surfaces. NQO1-induced secretion of PPIA engages CD147 on neutrophils, triggering NET formation and neutrophil elastase release, which promotes breast cancer lung metastasis. Co-immunoprecipitation, oxidation protection assay, gene knockdown/overexpression, in vivo lung metastasis mouse model, pharmacological PPIA inhibition Cancer research Medium 39073320
2022 NQO1 binds to PKLR (pyruvate kinase liver/red blood cell isoform), activates AMPK and AKT/mTOR signaling, and induces glycolytic reprogramming in breast cancer cells, promoting proliferation and metastasis. Co-immunoprecipitation (NQO1-PKLR), NQO1 overexpression/knockdown, glycolysis inhibitors (2-DG, 3-BrPA), pathway phosphorylation assays Cancer letters Medium 30954648
2020 NQO1 overexpression in HCC induces transcriptional activity of SREBP1 via a p53-dependent mechanism, which stabilizes Snail protein and promotes EMT and HCC metastasis. This NQO1/p53/SREBP1 axis regulates lipid metabolism in HCC progression. Luciferase reporter assay for SREBP1 transcription, NQO1 overexpression/knockdown, Western blot, immunohistochemistry Oncogene Medium 36253445
2018 NQO1 overexpression attenuates ROS and promotes GBM cell proliferation downstream of PTEN in glioblastoma. PTEN induces NQO1 expression, and NQO1 knockdown augments ROS and diminishes proliferation, while PINK1 overexpression represses ROS and inhibits proliferation, demonstrating paradoxical roles of NQO1 in GBM. Stable PTEN expression, NQO1 knockdown/overexpression, ROS measurement, cell proliferation assays Oxidative medicine and cellular longevity Medium 30595797
2020 C/EBPβ transcription factor binds to the promoters of NQO1 and GSTP1 and activates their expression in glioblastoma cells. C/EBPβ is upregulated by EGFR overexpression and drives GBM proliferation by neutralizing ROS via NQO1 and GSTP1 upregulation. Chromatin immunoprecipitation (ChIP) for C/EBPβ binding to NQO1 promoter, C/EBPβ knockdown/overexpression, ROS measurement, in vivo tumor growth assay Redox biology Medium 32526700
2019 Loss of NQO1 in corneal endothelial cells (FECD) exacerbates estrogen-DNA adduct formation and cell death. NQO1 neutralizes reactive estrogen metabolites (catechol estrogen 4-OHE2) and reduces ROS, protecting against DNA damage; NQO1 overexpression rescued cells from estrogen-induced damage, demonstrating a direct cytoprotective enzymatic role. NQO1 knockdown/overexpression, estrogen-DNA adduct assay, ROS measurement, cell viability assay, NAC rescue Free radical biology & medicine Medium 31857234
2016 A direct physical interaction between the dimeric naphthoquinone E6a and NQO1 was demonstrated by X-ray crystallography. The binding interface involves the isoalloxazine ring of the FAD cofactor and protein side chains in the active site. The compound affects the redox state of the FAD cofactor of NQO1. X-ray crystal structure of E6a-NQO1 complex, biochemical redox assays BMC structural biology High 26822308
2024 Serial crystallography determined the first structure of human NQO1 in complex with NADH, demonstrating that NADH binding decreases protein dynamics and stabilizes the dimer core and interface. Structural cooperativity between active sites is driven by long-range communication across the NQO1 homodimer structure. Serial X-ray crystallography (synchrotron), molecular dynamics simulations Protein science High 38501509
2014 NQO1 augments NAD+ levels in cochlear cells; β-lapachone, which acts through NQO1 to cycle NAD+/NADH, prevented cisplatin-mediated ototoxicity by restoring SIRT1 activity and reducing PARP-1 activation and p53-mediated microRNA-34a. β-Lapachone (NQO1 substrate) treatment, NAD+ measurement, SIRT1 activity assay, PARP-1 activation assay, in vitro and in vivo cisplatin ototoxicity model Cell death & disease Medium 24922076
2018 Overexpression of NQO1 (and CYB5R3) in transgenic mice enhances NAD+/sirtuin pathway activity, mimics aspects of caloric restriction including modest lifespan extension, improved metabolic flexibility, reduced inflammation, and protection against carcinogenesis. Transgenic mouse model overexpressing NQO1, metabolomics, lifespan assay, carcinogenesis models, NAD+ measurement Aging cell Medium 29706024
2020 NQO1 transgenic mice show NQO1-RNA interaction that mediates association with and inhibition of the translational machinery in skeletal muscle; NQO1 overexpression preserved glucose homeostasis and insulin sensitivity in high-fat diet conditions, correlating with distinct acetylation pattern of SIRT3 targets in intermediary metabolism. NQO1 transgenic mouse on high-fat diet, RNA interaction assays, quantitative mass spectrometry for protein acetylation, metabolomics NPJ aging and mechanisms of disease Medium 33298924
2024 NQO1 variants (particularly compound heterozygous or homozygous polymorphic forms) drastically reduce NQO1 protein levels, preventing efficient idebenone reduction. In its oxidized form, idebenone inhibits mitochondrial complex I; NQO1-dependent reduction is required for idebenone to bypass complex I and deliver electrons to complex III in LHON therapy. Patient cohort genotyping, idebenone reduction assay, respiratory function assays in patient cells, retrospective clinical outcome analysis Cell reports. Medicine Medium 38272025
2011 JNK kinase activation by ROS leads to stabilization of NRF2, which activates NQO1 expression. NQO1 in turn stabilizes TAp73 protein against 20S proteasomal degradation. JNK also directly phosphorylates TAp73 at multiple serine and threonine residues, promoting its dissociation from MDM2 and enhancing TAp73 transcriptional function. NRF2 stabilization assay, NQO1 induction assay, siRNA knockdown, withaferin A (WA) treatment, JNK inhibition, TAp73 co-IP with MDM2 Cell death & disease Medium 25341038
2024 DPP9 binds to KEAP1 and inhibits ubiquitin-mediated NRF2 degradation, increasing NRF2 protein stability, which promotes NQO1 mRNA transcription and reduces intracellular ROS, leading to chemoresistance in liver cancer cells. Co-immunoprecipitation (DPP9-KEAP1), NRF2 ubiquitination assay, NQO1 mRNA quantification, ROS measurement, chemotherapy sensitivity assay Redox biology Medium 39094401

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Archives of biochemistry and biophysics 561 20361926
2000 NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chemico-biological interactions 513 11154736
2007 Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free radical biology & medicine 365 17462537
2021 The diverse functionality of NQO1 and its roles in redox control. Redox biology 363 33774477
2017 Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch. Frontiers in physiology 249 28883796
1991 Human NAD(P)H:quinone oxidoreductase (NQO1) gene structure and induction by dioxin. Biochemistry 215 1657151
2011 NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochemical pharmacology 209 22209713
2002 NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review. Genetics in medicine : official journal of the American College of Medical Genetics 146 11882782
2014 Clinical implications of high NQO1 expression in breast cancers. Journal of experimental & clinical cancer research : CR 133 24499631
2015 Implications of NQO1 in cancer therapy. BMB reports 129 26424559
2020 Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx. Journal of hepatology 104 32987030
2002 Contribution of the NQO1 and GSTT1 polymorphisms to lung adenocarcinoma susceptibility. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 97 12163326
2006 NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 93 16702380
2022 Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth. British journal of cancer 89 35396498
2013 The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis. British journal of cancer 80 23860519
2015 Deoxynyboquinones as NQO1-Activated Cancer Therapeutics. Accounts of chemical research 78 26444384
2023 The Role of NQO1 in Ovarian Cancer. International journal of molecular sciences 69 37175546
2015 Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway. Toxicology letters 69 25680693
2008 NQO1 expression in pancreatic cancer and its potential use as a biomarker. Applied immunohistochemistry & molecular morphology : AIMM 68 18091324
2019 NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places. Bioscience reports 64 30518535
2019 Akt Phosphorylates NQO1 and Triggers its Degradation, Abolishing Its Antioxidative Activities in Parkinson's Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 31358653
2006 NQO1 and NQO2 regulation of humoral immunity and autoimmunity. The Journal of biological chemistry 61 16905546
2013 Efficient NQO1 substrates are potent and selective anticancer agents. ACS chemical biology 59 23937670
2008 NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review. Toxicology letters 59 18848868
2014 Augmentation of NAD(+) by NQO1 attenuates cisplatin-mediated hearing impairment. Cell death & disease 55 24922076
2014 Neophobia, NQO1 and SIRT1 as premorbid and prodromal indicators of AD in 3xTg-AD mice. Behavioural brain research 49 24837743
2015 Depleting Tumor-NQO1 Potentiates Anoikis and Inhibits Growth of NSCLC. Molecular cancer research : MCR 48 26553038
2022 The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability. Oncogene 47 36253445
2020 Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma. Journal of hematology & oncology 47 33087132
2019 The NQO1/PKLR axis promotes lymph node metastasis and breast cancer progression by modulating glycolytic reprogramming. Cancer letters 47 30954648
2021 Interactions of the antioxidant enzymes NAD(P)H: Quinone oxidoreductase 1 (NQO1) and NRH: Quinone oxidoreductase 2 (NQO2) with pharmacological agents, endogenous biochemicals and environmental contaminants. Chemico-biological interactions 44 34228969
2008 NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis. American journal of epidemiology 44 18945694
2011 Dynamics of Nrf2 and Keap1 in ARE-mediated NQO1 expression by wasabi 6-(methylsulfinyl)hexyl isothiocyanate. Journal of agricultural and food chemistry 43 22010800
2020 C/EBPβ mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation. Redox biology 42 32526700
2016 NQO1-Mediated Tumor-Selective Lethality and Radiosensitization for Head and Neck Cancer. Molecular cancer therapeutics 42 27196777
2018 NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress. Oxidative medicine and cellular longevity 41 30595797
1999 Identification of the Finnish founder mutation for diastrophic dysplasia (DTD). European journal of human genetics : EJHG 40 10482955
2022 Review on NAD(P)H dehydrogenase quinone 1 (NQO1) pathway. Molecular biology reports 37 35347544
2015 HIV-1 Rev downregulates Tat expression and viral replication via modulation of NAD(P)H:quinine oxidoreductase 1 (NQO1). Nature communications 37 26059226
2024 Impact of NQO1 dysregulation in CNS disorders. Journal of translational medicine 36 38167027
2019 NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma. Cell communication and signaling : CCS 36 31842909
2018 Redox modulation of NQO1. PloS one 35 29298345
2018 Overexpression of CYB5R3 and NQO1, two NAD+ -producing enzymes, mimics aspects of caloric restriction. Aging cell 33 29706024
2019 NQO1-dependent, Tumor-selective Radiosensitization of Non-small Cell Lung Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 32 30617135
2018 Alzheimer's Disease and NQO1: Is there a Link? Current Alzheimer research 32 28164770
2019 Loss of NQO1 generates genotoxic estrogen-DNA adducts in Fuchs Endothelial Corneal Dystrophy. Free radical biology & medicine 31 31857234
2021 Activation of AhR-NQO1 Signaling Pathway Protects Against Alcohol-Induced Liver Injury by Improving Redox Balance. Cellular and molecular gastroenterology and hepatology 30 34082111
2020 NQO1 protects obese mice through improvements in glucose and lipid metabolism. NPJ aging and mechanisms of disease 30 33298924
2016 Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms. Current drug targets 30 26721407
2005 Functions and distribution of NQO1 in human bone marrow: potential clues to benzene toxicity. Chemico-biological interactions 30 15935810
1995 Transcriptional stimulation of the retina-specific QR1 gene upon growth arrest involves a Maf-related protein. Molecular and cellular biology 30 7565708
2014 JNK-NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress. Cell death & disease 29 25341038
2017 Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease. Oxidative medicine and cellular longevity 28 28785379
2016 Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation. Free radical biology & medicine 28 27515817
2023 A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression. Nature cancer 25 37169843
2023 Effect of allyl isothiocyanate on oxidative stress in COPD via the AhR / CYP1A1 and Nrf2 / NQO1 pathways and the underlying mechanism. Phytomedicine : international journal of phytotherapy and phytopharmacology 24 36996530
2019 Betulin-1,4-quinone hybrids: Synthesis, anticancer activity and molecular docking study with NQO1 enzyme. European journal of medicinal chemistry 24 31158746
2023 A Novel NQO1 Enzyme-Responsive Polyurethane Nanocarrier for Redox-Triggered Intracellular Drug Release. Biomacromolecules 23 37040694
2018 Effect of β-Eudesmol on NQO1 suppression-enhanced sensitivity of cholangiocarcinoma cells to chemotherapeutic agents. BMC pharmacology & toxicology 23 29914576
2015 Nanotechnology-enabled delivery of NQO1 bioactivatable drugs. Journal of drug targeting 23 26453163
2006 Targeting NAD(P)H:Quinone Oxidoreductase (NQO1) in Pancreatic Cancer. Molecular carcinogenesis 23 28639725
2024 Targeting NQO1 induces ferroptosis and triggers anti-tumor immunity in immunotherapy-resistant KEAP1-deficient cancers. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 22 39490240
2022 Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles. Journal of controlled release : official journal of the Controlled Release Society 22 35618186
2015 Induction of NQO1 and Neuroprotection by a Novel Compound KMS04014 in Parkinson's Disease Models. Journal of molecular neuroscience : MN 22 25702135
2013 Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins. Biochemical and biophysical research communications 22 23692925
2024 Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy. Cell reports. Medicine 21 38272025
2012 A functional NQO1 609C>T polymorphism and risk of gastrointestinal cancers: a meta-analysis. PloS one 21 22272361
2000 Immunohistochemical localization of NQO1 in epithelial dysplasia and neoplasia and in donor eyes. Investigative ophthalmology & visual science 21 10845577
2016 A direct interaction between NQO1 and a chemotherapeutic dimeric naphthoquinone. BMC structural biology 20 26822308
2013 CYP2E1 and NQO1 genotypes and bladder cancer risk in a Lebanese population. International journal of molecular epidemiology and genetics 20 24319536
1993 Transcriptional downregulation of the retina-specific QR1 gene by pp60v-src and identification of a novel v-src-responsive unit. Molecular and cellular biology 20 8388536
2022 Ruscogenins Improve CD-Like Enteritis by Inhibiting Apoptosis of Intestinal Epithelial Cells and Activating Nrf2/NQO1 Pathway. Oxidative medicine and cellular longevity 19 35308175
2021 Nrf2‑Keap1‑ARE‑NQO1 signaling attenuates hyperoxia‑induced lung cell injury by inhibiting apoptosis. Molecular medicine reports 19 33495821
2024 NQO1 Triggers Neutrophil Recruitment and NET Formation to Drive Lung Metastasis of Invasive Breast Cancer. Cancer research 18 39073320
2024 DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells. Redox biology 18 39094401
2021 Chlamydia trachomatis Pgp3 protein regulates oxidative stress via activation of the Nrf2/NQO1 signal pathway. Life sciences 18 33891941
2017 Enhanced glycometabolism as a mechanism of NQO1 potentiated growth of NSCLC revealed by metabolomic profiling. Biochemical and biophysical research communications 18 29291405
2015 NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation. Scientific reports 18 25586669
2022 Research advances in NQO1-responsive prodrugs and nanocarriers for cancer treatment. Future medicinal chemistry 17 35102756
2022 DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway. Cell communication and signaling : CCS 17 36303144
2020 Discovery of Isoplumbagin as a Novel NQO1 Substrate and Anti-Cancer Quinone. International journal of molecular sciences 17 32575541
2019 Negative Cooperativity in NAD(P)H Quinone Oxidoreductase 1 (NQO1). Chembiochem : a European journal of chemical biology 17 31165578
2019 Tumor Suppressive Function of NQO1 in Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 17 31886179
2003 NAD(P)H: quinone oxidoreductase (NQO1) gene polymorphism and schizophrenia. Psychiatry research 17 12834817
2024 Human NQO1 as a Selective Target for Anticancer Therapeutics and Tumor Imaging. Cells 16 39120303
2021 Docosahexanoic acid signals through the Nrf2-Nqo1 pathway to maintain redox balance and promote neurite outgrowth. Molecular biology of the cell 16 33502893
2020 Combination of lapatinib and luteolin enhances the therapeutic efficacy of lapatinib on human breast cancer through the FOXO3a/NQO1 pathway. Biochemical and biophysical research communications 16 32800546
2020 Synthesis and biological evaluation of NQO1-activated prodrugs of podophyllotoxin as antitumor agents. Bioorganic & medicinal chemistry 16 33091789
2013 Protease-activated receptor-2 activates NQO-1 via Nrf2 stabilization in keratinocytes. Journal of dermatological science 16 24326025
2024 Structural dynamics and functional cooperativity of human NQO1 by ambient temperature serial crystallography and simulations. Protein science : a publication of the Protein Society 15 38501509
2022 Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1. Journal of personalized medicine 15 35629169
2018 A discriminator code-based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria. eLife 15 30091703
2014 The NQO1 C609T polymorphism and hepatocellular carcinoma risk. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 24532470
2013 CYP1A1, GSTM1, GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men. World journal of gastroenterology 15 23840148
2011 Dyrk1a activates antioxidant NQO1 expression through an ERK1/2-Nrf2 dependent mechanism. Molecular genetics and metabolism 15 22178546
2024 Daphnetin induces ferroptosis in ovarian cancer by inhibiting NAD(P)H:Quinone oxidoreductase 1 (NQO1). Phytomedicine : international journal of phytotherapy and phytopharmacology 14 39032284
2022 Switching a conflicted bacterial DTD-tRNA code is essential for the emergence of mitochondria. Science advances 14 35020439
2022 Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations. Antioxidants (Basel, Switzerland) 14 35740007
2022 Albumin binding revitalizes NQO1 bioactivatable drugs as novel therapeutics for pancreatic cancer. Journal of controlled release : official journal of the Controlled Release Society 14 35907592
2022 NQO-1 Enzyme-Activated NIR Theranostic Agent for Pancreatic Cancer. Analytical chemistry 13 35916489