Affinage

NQO1

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

Audit flag: ungrounded claim
Length
274 aa
Mass
30.9 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NQO1 is a homodimeric FAD-dependent flavoprotein that catalyzes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes using NADH or NADPH, preventing semiquinone formation and redox cycling (PMID:20361926); this reductase activity extends to ubiquinone and vitamin E quinone within a plasma-membrane redox system and, at high expression, to direct superoxide reduction (PMID:33774477), and it makes NQO1 an efficient intracellular generator of NAD+ for downstream NAD+-dependent enzymes such as PARP and sirtuins (PMID:33774477, PMID:28883796). Crystallographic and biophysical work shows that NADH binding rigidifies the dimer core and interface and that the two active sites communicate through long-range allosteric coupling involving buried N-terminal leucine residues, producing negative cooperativity (PMID:38501509, PMID:35740007). Beyond catalysis, NQO1 acts as a redox-sensitive gatekeeper that physically binds intrinsically disordered or unstructured regions of client proteins and shields them from 20S/26S proteasomal degradation, stabilizing p53, HIF-1α (via competition with PHD at its ODD), c-Fos, SIRT6, and the viral HBx protein, with downstream consequences for senescence, hypoxic signaling, cell-cycle progression, apoptosis evasion, and viral cccDNA transcription (PMID:20361926, PMID:26424559, PMID:26078718, PMID:27966538, PMID:36793872, PMID:31842909, PMID:32987030). NQO1 also binds SERPINA1 mRNA to promote α-1-antitrypsin translation (PMID:27515817) and contributes to redox-dependent regulation of inflammation by promoting PDLIM2-dependent degradation of IκB-ζ to restrain TLR-driven cytokine induction (PMID:29334320). Its own abundance is controlled by Akt phosphorylation at T128, which recruits Parkin as the E3 ligase for proteasomal turnover (PMID:31358653). The pharmacological corollary of its reductase activity is striking: NQO1-mediated bioactivation of β-lapachone drives a futile redox cycle that selectively kills NQO1-high cancer cells through ROS, PARP-1 hyperactivation, and NAD+/ATP depletion (PMID:17609380, PMID:31324798).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 Medium

    Established how NQO1 transcription is controlled during cell-state transitions, linking its induction to growth arrest and oncogenic signaling rather than constitutive expression.

    Evidence CAT reporter, EMSA, antibody supershift and ectopic c-maf/mafB expression with a temperature-sensitive v-src system in avian retinal cells

    PMID:7565708

    Open questions at the time
    • Identified the activator only as a Maf-related C1 complex in an avian model
    • Does not address human promoter regulation
  2. 2006 Medium

    Demonstrated that loss of NQO1 produces in vivo immune defects coupled to NADH accumulation, framing NQO1 as a determinant of intracellular redox state with physiological consequences.

    Evidence NQO1-null mice with FACS, germinal center and collagen-induced arthritis assays plus cofactor measurement

    PMID:16905546

    Open questions at the time
    • Mechanism connecting NADH accumulation to NF-κB and B-cell phenotypes not resolved
    • Single lab study
  3. 2007 High

    Showed that NQO1's reductase activity can be turned into a cytotoxic liability, defining the mechanistic basis for NQO1-targeted quinone therapy in cancer.

    Evidence Isogenic NQO1+/− lines with PARP-inhibitor and Ca2+-chelator rescue, ROS measurement, and dicoumarol inhibition

    PMID:17609380

    Open questions at the time
    • Does not address determinants of NQO1 expression heterogeneity in tumors
  4. 2010 High

    Consolidated the obligatory 2-electron reductase mechanism and introduced the gatekeeper concept, establishing that NQO1 both detoxifies quinones and physically stabilizes p53 against the 20S proteasome.

    Evidence Enzyme assays plus reciprocal Co-IP and proteasome degradation/loss-of-function experiments

    PMID:20361926 PMID:26078718 PMID:26424559

    Open questions at the time
    • Structural basis of client recognition not defined
    • Generality across disordered clients not yet tested
  5. 2015 Medium

    Extended the gatekeeper role to senescence and tumor survival, showing NQO1 stabilizes p53 in an MDM2/ubiquitin-independent manner and supports a pro-survival program beyond detoxification.

    Evidence NQO1 depletion/ectopic expression during oncogene-induced senescence; siRNA knockdown with anoikis, anchorage-independent growth and xenograft assays

    PMID:26078718 PMID:26553038

    Open questions at the time
    • Whether p53 stabilization and ROS control are mechanistically separable not resolved
    • Single lab studies
  6. 2016 High

    Broadened NQO1's molecular repertoire to oxygen-independent HIF-1α stabilization and to mRNA-binding translational control, showing it operates on both protein and RNA clients.

    Evidence Co-IP and PHD competition assays for HIF-1α; RIP, biotin pulldown, polysome profiling, luciferase reporter and NQO1-KO mice for SERPINA1 mRNA

    PMID:27515817 PMID:27966538

    Open questions at the time
    • RNA-binding determinants on NQO1 not mapped
    • Scope of the mRNA target set unknown
  7. 2018 Medium

    Linked NQO1's catalytic state to its protein-protein interactions and to inflammation control, defining a redox-sensitive conformational switch and a PDLIM2-dependent route to IκB-ζ degradation.

    Evidence Limited proteolysis and antibody epitope studies on purified NQO1 with SIRT2/acetyl-tubulin co-localization; Co-IP, NQO1-deficient macrophages and ubiquitination assays for IκB-ζ/PDLIM2

    PMID:29298345 PMID:29334320

    Open questions at the time
    • SIRT2/spindle NAD+ supply function inferred from co-localization, not directly proven
    • Whether conformational switching directly gates each client interaction untested
  8. 2019 Medium

    Identified the regulatory input controlling NQO1 abundance and added multiple disordered clients, tying Akt-Parkin turnover and client stabilization (c-Fos, SIRT6, PPIA) to proliferation, apoptosis evasion and metastasis.

    Evidence In vitro kinase assay with T128A mutant, ubiquitination and Co-IP with Parkin knockdown; Co-IP/pulldown, KD/OE, cell-cycle and in vivo tumor/metastasis models for the clients

    PMID:31358653 PMID:31842909 PMID:36793872 PMID:39073320

    Open questions at the time
    • Hierarchy and competition among the many clients unknown
    • Most client studies are single-lab
  9. 2020 Medium

    Demonstrated that NQO1 client stabilization is exploited by a viral protein, extending the gatekeeper function to HBx and chromatin-level control of viral transcription.

    Evidence Co-IP, NQO1 knockdown and dicoumarol treatment, ChIP and humanized liver mouse model

    PMID:32987030

    Open questions at the time
    • Generality across viral substrates untested
    • Single lab study
  10. 2021 Medium

    Integrated NQO1 into NAD+ metabolism and metabolic protection, showing it generates NAD+ for sirtuins/PARP, partners SIRT1 under mitochondrial stress, and protects against diet-induced metabolic defects.

    Evidence Cellular NAD+/NADH and PARP/sirtuin assays; Co-IP with SIRT1 dead-mutant controls; NQO1 transgenic mice on high-fat diet with metabolomics and proteomics

    PMID:28883796 PMID:33298924 PMID:33774477 PMID:34234670

    Open questions at the time
    • Whether NAD+ generation versus protein/RNA chaperoning drives metabolic protection not disentangled
    • Subcellular site of NAD+ delivery unclear
  11. 2024 High

    Provided the structural and biophysical mechanism of NQO1 cooperativity, showing NADH binding rigidifies the dimer and that buried N-terminal leucines mediate long-range allosteric coupling between active sites.

    Evidence Serial crystallography of the hNQO1-NADH complex with MD simulations; site-directed mutagenesis with FAD-binding and differential scanning fluorimetry readouts

    PMID:35740007 PMID:38501509

    Open questions at the time
    • Does not connect allostery to the protein/RNA chaperone functions
    • Physiological role of negative cooperativity untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single flavoprotein coordinates its reductase chemistry, NAD+ ratio sensing, and the selection among numerous disordered protein and mRNA clients remains unresolved.
  • No unified structural model of client binding versus catalysis
  • Determinants of client specificity and competition not defined
  • In vivo relevance of individual client interactions largely from single studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016491 oxidoreductase activity 3 GO:0003723 RNA binding 2 GO:0140313 molecular sequestering activity 2 GO:0016209 antioxidant activity 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
FOSHBXHIF1ANFKBIZPPIASIRT1SIRT6TP53

Evidence

Reading pass · 28 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 either NADH or NADPH as cofactors, thereby preventing semiquinone formation and redox cycling. Biochemical enzyme assays, review of accumulated in vitro data Archives of biochemistry and biophysics High 20361926
2010 NQO1 binds to and stabilizes the tumor suppressor p53 against proteasomal degradation, functioning as a 'gatekeeper' that inhibits 20S proteasome-mediated degradation of specific intrinsically disordered proteins. Co-immunoprecipitation, proteasome degradation assays, loss-of-function experiments Archives of biochemistry and biophysics High 20361926 26078718 26424559
2007 NQO1-mediated 2-electron reduction of β-lapachone triggers a futile redox cycle generating massive ROS, leading to PARP-1 hyperactivation, NAD+/ATP depletion, calpain activation, and programmed necrosis selectively in NQO1-expressing cancer cells. Isogenic NQO1+ vs NQO1− cell lines, PARP inhibitor rescue, Ca2+ chelator rescue, ROS measurements, pharmacological inhibition with dicoumarol Proceedings of the National Academy of Sciences of the United States of America High 17609380
2016 NQO1 directly binds the oxygen-dependent degradation domain (ODD) of HIF-1α and inhibits PHD-mediated priming of HIF-1α for proteasomal degradation, thereby stabilizing HIF-1α protein levels independently of oxygen. Co-immunoprecipitation, NQO1 knockdown in cancer cell lines, HIF-1α stability assays, competition binding assays with PHD Nature communications High 27966538
2019 Akt phosphorylates NQO1 at threonine 128, triggering its polyubiquitination and proteasomal degradation, with Parkin functioning as the E3 ubiquitin ligase in this process. In vitro kinase assay, site-directed mutagenesis (T128A unphosphorylatable mutant), Co-IP, ubiquitination assay, Parkin knockdown The Journal of neuroscience High 31358653
2018 NQO1 interacts with the nuclear IκB protein IκB-ζ and promotes its ubiquitin-dependent degradation by augmenting the association between the E3 ligase PDLIM2 and IκB-ζ, thereby suppressing TLR-mediated induction of selective cytokines including IL-6. Co-immunoprecipitation, NQO1-deficient macrophages, ubiquitination assays, LPS stimulation assays The Journal of experimental medicine High 29334320
2016 NQO1 binds SERPINA1 mRNA at its 3'UTR and coding region and promotes translation of α-1-antitrypsin (A1AT) without affecting mRNA stability; NQO1 knockout mice show reduced hepatic and serum A1AT and increased neutrophil elastase activity. Ribonucleoprotein immunoprecipitation (RIP), microarray, biotin pulldown, polysome profiling, luciferase reporter assay, NQO1-KO mouse model Free radical biology & medicine High 27515817
2018 NQO1 undergoes a conformational change upon NAD(P)H binding that occludes its C-terminal domain and helix 7 epitopes; under oxidizing conditions (NAD(P)+ form), these epitopes are re-exposed. In cells, NQO1 co-localizes with acetyl α-tubulin and SIRT2 on centrosomes, the mitotic spindle, and midbody during cell division, suggesting NQO1 provides NAD+ for SIRT2-mediated microtubule deacetylation. Purified NQO1 structural studies with limited proteolysis and antibody immunoreactivity, β-lapachone treatment to oxidize NAD(P)H, immunostaining co-localization with Sirt2 and acetyl-tubulin PloS one Medium 29298345
2021 NQO1 physically interacts with SIRT1 (but not enzymatically dead SIRT1 H363Y mutant), and this interaction is enhanced under mitochondrial stress with concomitant nuclear accumulation of NQO1; NQO1 depletion compromises SIRT1-mediated target gene induction and SIRT1's protective role during mitochondrial inhibition. Co-immunoprecipitation (including dead-mutant controls), NQO1 knockdown, target gene expression assays, mitochondrial inhibition Frontiers in pharmacology Medium 34234670
2019 NQO1 stabilizes PPIA (peptidyl-prolyl cis-trans isomerase A) by preventing oxidation at cysteine C161; NQO1-stabilized PPIA activates CD147 and is secreted to engage CD147 on neutrophils, triggering NET and neutrophil elastase release that promotes breast cancer lung metastasis. Co-immunoprecipitation, knockdown/overexpression, pharmacological inhibition of PPIA, in vivo metastasis models Cancer research Medium 39073320
2019 NQO1-mediated bioactivation of β-lapachone generates ROS in NQO1-high tumor cells, inducing HMGB1 release, which activates host TLR4/MyD88/type I interferon signaling and Batf3 dendritic cell-dependent cross-priming to stimulate adaptive anti-tumor immunity. NQO1-positive vs NQO1-negative isogenic cells, TLR4/MyD88 knockout models, HMGB1 neutralization, β-lapachone treatment in vivo Nature communications Medium 31324798
2013 NQO1 protein localizes not only to cytosol but also to endoplasmic reticulum membranes and mitochondria; targeting to mitochondrial or ER membranes is independent of CYP1A1 presence in those membranes. Subcellular fractionation, knockout mouse lines (Nqo1−/−, Cyp1a1 knock-in variants), Western blotting of fractions Biochemical and biophysical research communications Medium 23692925
2019 NQO1 directly interacts with c-Fos at its unstructured DNA-binding domain, inhibiting proteasome-mediated degradation of c-Fos, thereby inducing CKS1 expression and promoting cell cycle progression at the G2/M phase. Co-immunoprecipitation, pull-down assays, siRNA knockdown, overexpression systems, cell cycle synchronization and flow cytometry, CDK1 kinase assays Theranostics Medium 36793872
2019 NQO1 potentiates apoptosis evasion in hepatocellular carcinoma by binding SIRT6 and inhibiting its ubiquitin-mediated 26S proteasomal degradation; stabilized SIRT6 reduces AKT acetylation, increasing AKT phosphorylation/activity, which phosphorylates XIAP at Ser87 to stabilize the anti-apoptotic protein. Immunoprecipitation, NQO1 knockout, SIRT6/AKT overexpression rescue experiments, orthotopic mouse tumor model Cell communication and signaling Medium 31842909
2020 NQO1 binds to HBx protein and protects it from 20S proteasome-mediated degradation; NQO1 knockdown or dicoumarol treatment promotes HBx degradation, reduces HBx recruitment to cccDNA, and establishes a repressive chromatin state to inhibit cccDNA transcription. Immunoprecipitation, NQO1 knockdown, dicoumarol (NQO1 inhibitor) treatment, chromatin immunoprecipitation, humanized liver mouse model Journal of hepatology Medium 32987030
2015 NQO1 depletion in NQO1-overexpressing lung adenocarcinoma cells increases ROS, inhibits anchorage-independent growth, sensitizes cells to anoikis, decreases 3D tumor spheroid invasion, and reduces ALDH-high cancer stem cell populations, demonstrating a pro-survival function of NQO1 in tumor cells beyond antioxidant detoxification. siRNA knockdown of NQO1, ROS measurement, anoikis assay, anchorage-independent growth assay, xenograft models Molecular cancer research Medium 26553038
2015 NQO1 promotes accumulation of p53 during oncogene-induced senescence (OIS) in an MDM2- and ubiquitin-independent manner, reinforcing the cellular senescence phenotype; NQO1 expression during OIS is regulated by NRF2/KEAP1 signaling. NQO1 depletion and ectopic expression during OIS, p53 stability assays, MDM2 independence confirmed, NRF2/KEAP1 pathway analysis International journal of biological sciences Medium 26078718
2006 NQO1-null mice show decreased B-cells, lower germinal center responses, altered B-cell homing, impaired immune responses, and susceptibility to autoimmunity with decreased NF-κB expression/activation; these defects are accompanied by accumulation of NADH (NQO1 cofactor), indicating altered intracellular redox status underlies the immune phenotype. NQO1-null mice, FACS for B-cell populations, germinal center assays, collagen-induced arthritis model, microarray for chemokines The Journal of biological chemistry Medium 16905546
2021 NQO1 overexpression in vivo (transgenic mice) produces NQO1-RNA complexes that associate with and inhibit the translational machinery in skeletal muscle, contributes to NAD+ generation, and protects against diet-induced metabolic defects including insulin resistance and dyslipidemia. NQO1 transgenic mice, high-fat diet model, RNA-binding assays, metabolomics, label-free quantitative mass spectrometry, acetylation proteomics NPJ aging and mechanisms of disease Medium 33298924
2024 Serial crystallography determined the first structure of human NQO1 in complex with NADH, revealing that NADH binding decreases protein dynamics and stabilizes hNQO1 especially at the dimer core and interface; structural analysis provides first evidence that functional cooperativity is driven by long-range structural communication between active sites. Serial crystallography at synchrotron, molecular dynamics simulations, structure determination of hNQO1-NADH complex Protein science High 38501509
2016 Crystal structure of NQO1 in complex with a dimeric naphthoquinone (E6a) revealed direct physical interaction between E6a and the isoalloxazine ring of the FAD cofactor plus protein active-site residues; biochemical evidence showed the compound affects the redox state of the FAD cofactor. X-ray crystallography (first structure of dimeric naphthoquinone-NQO1 complex), FAD redox state biochemical assays BMC structural biology High 26822308
2021 NQO1 functions as a component of the plasma membrane redox system, performing 2-electron reduction of ubiquinone and vitamin E quinone to generate their antioxidant forms; at high expression levels NQO1 also acts as a direct superoxide reductase. In vitro enzyme assays with ubiquinone/vitamin E quinone substrates, superoxide scavenging assays Redox biology Medium 33774477
2021 NQO1 serves as an efficient intracellular generator of NAD+ for NAD+-dependent enzymes including PARP and sirtuins; this NAD+ generating function is relevant to metabolic regulation. Cellular NAD+/NADH measurements, NQO1 overexpression and knockout studies, PARP/sirtuin activity assays Redox biology Medium 28883796 33774477
2015 NQO1 expression is regulated transcriptionally by C/EBPβ, which binds the NQO1 promoter; C/EBPβ is upregulated by EGFR overexpression and drives NQO1 expression to reduce ROS and promote glioblastoma cell proliferation. ChIP (promoter binding), siRNA knockdown of C/EBPβ, overexpression, ROS measurements, in vivo tumor growth Redox biology Medium 32526700
1995 Transcription of QR1 (NQO1) in avian neural retina is stimulated upon growth arrest/differentiation via a cis-acting A-box element that binds a Maf-related protein (C1 complex); v-Src activity downregulates QR1 transcription by suppressing C1 complex formation. CAT reporter transfection assays in quail retinal cells, gel-shift (EMSA) assays, antibody supershift with Maf antibodies, ectopic expression of c-maf/mafB cDNAs, temperature-sensitive v-src mutant system Molecular and cellular biology Medium 7565708
2015 NQO1 activates AMPK in an NQO1-dependent manner under oxygen-glucose deprivation (OGD), suppressing mTOR/S6K/4E-BP1 survival signaling; mechanistically, NQO1 triggers CD38/cADPR/RyR-mediated intracellular Ca2+ release, activating CaMKII which then activates AMPK. NQO1 siRNA knockdown, AMPK/mTOR pathway analysis, Ca2+ signaling inhibitors (RyR blocker, CaMKII inhibitor), CD38 knockdown, OGD cell model Scientific reports Medium 25586669
2021 Alcohol consumption induces AhR activation which transcriptionally induces NQO1 expression; separately, decreased cellular NAD+/NADH ratio (not AhR) triggers nuclear translocation of NQO1; NQO1 overexpression prevents alcohol-induced hepatic NAD+ depletion and reverses liver injury. Hepatocyte-specific AhR knockout mice, NQO1 overexpression mouse model, cellular fractionation, NAD+/NADH measurement, in vitro cell studies Cellular and molecular gastroenterology and hepatology Medium 34082111
2024 NQO1 exhibits negative cooperativity between its two active sites, mediated by long-range allosteric communication through the dimer interface; buried leucine residues (L7, L10, L30) in the N-terminal domain contribute to this allostery, with L10A severely decreasing FAD binding affinity (~20-fold) through long-range effects on the FAD binding site. Site-directed mutagenesis, FAD binding affinity measurements, conformational stability assays (differential scanning fluorimetry), mass spectrometry, molecular dynamics simulations Antioxidants Medium 35740007

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 566 20361926
2000 NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chemico-biological interactions 513 11154736
2021 The diverse functionality of NQO1 and its roles in redox control. Redox biology 375 33774477
2007 Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free radical biology & medicine 366 17462537
2007 An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone. Proceedings of the National Academy of Sciences of the United States of America 291 17609380
2017 Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch. Frontiers in physiology 250 28883796
2011 NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochemical pharmacology 209 22209713
2016 NQO1 inhibits proteasome-mediated degradation of HIF-1α. Nature communications 148 27966538
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
2007 Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential. Organic & biomolecular chemistry 106 18264564
2020 Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx. Journal of hepatology 104 32987030
2022 Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth. British journal of cancer 94 35396498
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
2005 NQO1, MPO, and the risk of lung cancer: a HuGE review. Genetics in medicine : official journal of the American College of Medical Genetics 86 16170238
2013 The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a comprehensive meta-analysis. British journal of cancer 81 23860519
2015 Deoxynyboquinones as NQO1-Activated Cancer Therapeutics. Accounts of chemical research 78 26444384
2019 NQO1 targeting prodrug triggers innate sensing to overcome checkpoint blockade resistance. Nature communications 77 31324798
2023 The Role of NQO1 in Ovarian Cancer. International journal of molecular sciences 69 37175546
2008 NQO1 expression in pancreatic cancer and its potential use as a biomarker. Applied immunohistochemistry & molecular morphology : AIMM 68 18091324
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 66 31358653
2019 NAD(P)H quinone oxidoreductase (NQO1): an enzyme which needs just enough mobility, in just the right places. Bioscience reports 64 30518535
2006 NQO1 and NQO2 regulation of humoral immunity and autoimmunity. The Journal of biological chemistry 62 16905546
2013 Efficient NQO1 substrates are potent and selective anticancer agents. ACS chemical biology 60 23937670
2008 NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review. Toxicology letters 59 18848868
2022 The NQO1/p53/SREBP1 axis promotes hepatocellular carcinoma progression and metastasis by regulating Snail stability. Oncogene 49 36253445
2020 Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma. Journal of hematology & oncology 49 33087132
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
2019 The NQO1/PKLR axis promotes lymph node metastasis and breast cancer progression by modulating glycolytic reprogramming. Cancer letters 47 30954648
2020 Modulation of Nqo1 activity intercepts anoikis resistance and reduces metastatic potential of hepatocellular carcinoma. Cancer science 46 31968140
2018 NQO1 inhibits the TLR-dependent production of selective cytokines by promoting IκB-ζ degradation. The Journal of experimental medicine 46 29934320
2011 Dynamics of Nrf2 and Keap1 in ARE-mediated NQO1 expression by wasabi 6-(methylsulfinyl)hexyl isothiocyanate. Journal of agricultural and food chemistry 46 22010800
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 45 34228969
2008 NQO1 polymorphisms and de novo childhood leukemia: a HuGE review and meta-analysis. American journal of epidemiology 44 18945694
2020 C/EBPβ mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation. Redox biology 43 32526700
2018 NQO1 Is Regulated by PTEN in Glioblastoma, Mediating Cell Proliferation and Oxidative Stress. Oxidative medicine and cellular longevity 43 30595797
2016 NQO1-Mediated Tumor-Selective Lethality and Radiosensitization for Head and Neck Cancer. Molecular cancer therapeutics 42 27196777
2019 NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma. Cell communication and signaling : CCS 38 31842909
2024 Impact of NQO1 dysregulation in CNS disorders. Journal of translational medicine 37 38167027
2022 Review on NAD(P)H dehydrogenase quinone 1 (NQO1) pathway. Molecular biology reports 37 35347544
2018 Redox modulation of NQO1. PloS one 35 29298345
2018 Alzheimer's Disease and NQO1: Is there a Link? Current Alzheimer research 33 28164770
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
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
2017 Expression of the NRF2 Target Gene NQO1 Is Enhanced in Mononuclear Cells in Human Chronic Kidney Disease. Oxidative medicine and cellular longevity 29 28785379
2014 JNK-NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress. Cell death & disease 29 25341038
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 28 36996530
2016 Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation. Free radical biology & medicine 28 27515817
2023 A Novel NQO1 Enzyme-Responsive Polyurethane Nanocarrier for Redox-Triggered Intracellular Drug Release. Biomacromolecules 26 37040694
2023 A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression. Nature cancer 26 37169843
2008 Association of the NQO1, MPO, and XRCC1 polymorphisms and chromosome damage among workers at a petroleum refinery. Journal of toxicology and environmental health. Part A 26 18214807
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 25 39490240
2023 NQO1 regulates cell cycle progression at the G2/M phase. Theranostics 24 36793872
2022 Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles. Journal of controlled release : official journal of the Controlled Release Society 24 35618186
2019 Betulin-1,4-quinone hybrids: Synthesis, anticancer activity and molecular docking study with NQO1 enzyme. European journal of medicinal chemistry 24 31158746
2015 Nanotechnology-enabled delivery of NQO1 bioactivatable drugs. Journal of drug targeting 23 26453163
2013 Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins. Biochemical and biophysical research communications 23 23692925
2006 Targeting NAD(P)H:Quinone Oxidoreductase (NQO1) in Pancreatic Cancer. Molecular carcinogenesis 23 28639725
2024 Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy. Cell reports. Medicine 22 38272025
2024 NQO1 Triggers Neutrophil Recruitment and NET Formation to Drive Lung Metastasis of Invasive Breast Cancer. Cancer research 22 39073320
2015 Induction of NQO1 and Neuroprotection by a Novel Compound KMS04014 in Parkinson's Disease Models. Journal of molecular neuroscience : MN 22 25702135
2015 NQO1 Stabilizes p53 in Response to Oncogene-Induced Senescence. International journal of biological sciences 22 26078718
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
2024 PIM1 alleviated liver oxidative stress and NAFLD by regulating the NRF2/HO-1/NQO1 pathway. Life sciences 20 38735366
2024 DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells. Redox biology 20 39094401
2024 Human NQO1 as a Selective Target for Anticancer Therapeutics and Tumor Imaging. Cells 20 39120303
2022 Ruscogenins Improve CD-Like Enteritis by Inhibiting Apoptosis of Intestinal Epithelial Cells and Activating Nrf2/NQO1 Pathway. Oxidative medicine and cellular longevity 20 35308175
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
2011 NQO1 expression correlates inversely with NFκB activation in human breast cancer. Breast cancer research and treatment 20 21706157
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
1980 Assignment of a structural gene for a fourth human diaphorase (DIA4) to chromosome 16 in man-mouse somatic cell hybrids. Human genetics 20 6928411
2021 Nrf2‑Keap1‑ARE‑NQO1 signaling attenuates hyperoxia‑induced lung cell injury by inhibiting apoptosis. Molecular medicine reports 19 33495821
2021 Chlamydia trachomatis Pgp3 protein regulates oxidative stress via activation of the Nrf2/NQO1 signal pathway. Life sciences 18 33891941
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
2019 Tumor Suppressive Function of NQO1 in Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 17 31886179
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 Synthesis and biological evaluation of NQO1-activated prodrugs of podophyllotoxin as antitumor agents. Bioorganic & medicinal chemistry 16 33091789
2011 Dyrk1a activates antioxidant NQO1 expression through an ERK1/2-Nrf2 dependent mechanism. Molecular genetics and metabolism 16 22178546
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
2024 Daphnetin induces ferroptosis in ovarian cancer by inhibiting NAD(P)H:Quinone oxidoreductase 1 (NQO1). Phytomedicine : international journal of phytotherapy and phytopharmacology 15 39032284
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
2022 Albumin binding revitalizes NQO1 bioactivatable drugs as novel therapeutics for pancreatic cancer. Journal of controlled release : official journal of the Controlled Release Society 15 35907592
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
2022 Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations. Antioxidants (Basel, Switzerland) 14 35740007
2021 NQO1 Binds and Supports SIRT1 Function. Frontiers in pharmacology 14 34234670
2024 Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling. Cancer research 13 39264695
2023 NQO1 drives glioblastoma cell aggressiveness through EMT induction via the PI3K/Akt/mTOR/Snail pathway. International journal of oncology 13 37594082
2013 NQO1 C609T polymorphism and esophageal cancer risk: a HuGE review and meta-analysis. BMC medical genetics 13 23497461

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