Affinage

PRDX6

Peroxiredoxin-6 · UniProt P30041

Length
224 aa
Mass
25.0 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRDX6 is a bifunctional antioxidant enzyme that protects cells from oxidative and lipid-peroxidation damage through two independent catalytic activities housed in distinct active sites: a glutathione-dependent peroxidase centered on Cys47 (PVCTTE motif) and a Ca2+-independent acidic phospholipase A2 (iPLA2) centered on Ser32 (GDSWG motif), with the S32A and C47S mutants selectively abolishing one activity each (PMID:10893423). Unlike 2-Cys peroxiredoxins, regeneration of the oxidized Cys47 peroxidatic cysteine requires heterodimerization with GSH-loaded piGST (GSTπ), which glutathionylates Cys47 to permit reduction of the mixed disulfide and restore peroxidase activity at a 1:1 stoichiometry (PMID:15004285, PMID:15890616). Functionally, PRDX6 reduces phospholipid hydroperoxides and H2O2 using GSH as the electron donor, preventing accumulation of phosphatidylcholine hydroperoxides, lipid peroxidation, and apoptosis, with Prdx6-null mice showing heightened sensitivity to hyperoxia and paraquat and adenoviral PRDX6 protecting lungs (PMID:12372839, PMID:12193653, PMID:15890616). The two activities are reciprocally and post-translationally tuned: irreversible hyperoxidation of Cys47 to sulfinic acid paradoxically activates iPLA2 and drives G2/M arrest with p53/p21 upregulation (PMID:18826942), SUMO1 conjugation at Lys122/Lys142 lowers abundance and both activities (PMID:28055018, PMID:24910119), and MAPK-mediated phosphorylation at Thr177 supports optimal iPLA2 (PMID:38287382). Through its iPLA2 activity PRDX6 acts as a positive regulator of NADPH oxidase ROS output—binding and stabilizing Nox1/Noxa1 components and supporting RAC-dependent NOX2 maturation—thereby coupling phospholipid metabolism to redox signaling, cell migration, and inflammatory responses (PMID:27094494, PMID:22678913, PMID:37030053). Independently of its enzymatic redox chemistry, PRDX6 functions as a selenium-acceptor protein that reacts with selenide and interacts with SEPHS2 to feed selenocysteyl-tRNA synthesis, supporting efficient GPX4 and selenoprotein expression; loss of PRDX6 lowers GPX4 and sensitizes cells to ferroptosis, and this selenium-delivery role—rather than direct PLOOH reduction—accounts for its ferroptosis-suppressing effect (PMID:38867112, PMID:39547224, PMID:39547222). PRDX6 transcription is governed by Sp1, Nrf2/ARE, Bmal1 E-box, and Klf9 repressor elements, integrating its expression with stress, circadian, and survival programs (PMID:22113199, PMID:31569690, PMID:32784474, PMID:29074861).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established that PRDX6 is a single protein carrying two mechanistically separable catalytic functions, defining the structural basis for its dual peroxidase and phospholipase activities.

    Evidence Site-directed mutagenesis (S32A, C47S) with recombinant enzyme assays and inhibitor mapping

    PMID:10893423

    Open questions at the time
    • Did not establish how the two activities are coordinated in vivo
    • No structural model of the bifunctional active-site arrangement
  2. 2004 High

    Resolved how the 1-Cys peroxidase regenerates its oxidized active site, showing it depends on a heterodimeric partner rather than an intramolecular resolving cysteine.

    Evidence In vitro heterodimerization with GSTπ at defined stoichiometry and liposome delivery into cells lacking the partner

    PMID:15004285

    Open questions at the time
    • Physiological regulation of GSTπ availability not addressed
    • Structural interface of the heterodimer not resolved
  3. 2005 High

    Quantified the catalytic mechanism and demonstrated its physiological relevance in protecting against oxidative lung injury.

    Evidence Kinetic in vitro assays plus Prdx6-null and adenoviral-overexpression mouse hyperoxia/paraquat models

    PMID:15890616

    Open questions at the time
    • Relative in vivo contribution of peroxidase vs iPLA2 to lung protection not separated
    • Tissue-specific substrate preferences unresolved
  4. 2002 High

    Showed in intact cells that PRDX6 prevents phospholipid hydroperoxide accumulation and apoptosis, defining its antioxidant role at the membrane level.

    Evidence Antisense knockdown and stable overexpression in lung epithelial cells with lipid peroxidation readouts and adenoviral rescue

    PMID:12193653 PMID:12372839

    Open questions at the time
    • Did not determine whether protection requires peroxidase, iPLA2, or both
    • GSH-dependence mechanism not dissected at the level of membrane repair
  5. 2008 High

    Revealed that irreversible hyperoxidation of the peroxidatic cysteine is not merely inactivating but switches PRDX6 toward enhanced iPLA2 activity and cell-cycle arrest, identifying a redox-driven activity switch.

    Evidence H2O2 treatment with anti-sulfinic acid immunoblot, iPLA2 assays, C47A/S32A mutants, and cell-cycle analysis

    PMID:18826942

    Open questions at the time
    • Structural basis of how Cys47 oxidation activates the distant Ser32 site unresolved
    • Reversibility/recovery pathway in vivo unclear
  6. 2017 High

    Identified SUMO1 conjugation at Lys122/142 and Thr177 phosphorylation as post-translational controls of PRDX6 abundance and dual activity.

    Evidence Site-directed mutagenesis with quantitative activity and stability assays in Prdx6-null complementation

    PMID:28055018

    Open questions at the time
    • SUMO ligase/protease responsible not identified here
    • Kinase responsible for T177 not defined in this study
  7. 2014 Medium

    Linked aberrant SUMOylation to reduced PRDX6 transcription via impaired Sp1, connecting post-translational modification to gene-level decline during stress and aging.

    Evidence Sumo1-fused constructs, CAT reporter and gel-shift assays, and SENP1 rescue in lens epithelial cells

    PMID:24910119

    Open questions at the time
    • Direct evidence that SUMOylated PRDX6 modulates Sp1 not fully mechanistic
    • Single cell-type context
  8. 2012 Medium

    Demonstrated that the iPLA2 activity, not peroxidase, is specifically required for PRDX6 to support agonist-stimulated NADPH oxidase activity in phagocytes.

    Evidence shRNA knockdown and rescue with active-site mutants in PLB-985 cells under fMLF vs PMA stimulation

    PMID:22678913

    Open questions at the time
    • Molecular link between iPLA2 product and oxidase assembly not defined
    • Agonist-specificity mechanism unexplained
  9. 2016 High

    Provided a physical-interaction mechanism for PRDX6 control of NADPH oxidase by showing it binds and stabilizes Noxa1/Nox1 components in an activity-dependent manner.

    Evidence Yeast two-hybrid, co-IP, mutant expression, MJ33 inhibition, and migration assays

    PMID:27094494

    Open questions at the time
    • Whether stabilization is direct or requires iPLA2 lipid products unresolved
    • Structural basis of the SH3 interaction not determined
  10. 2023 Medium

    Extended PRDX6 oxidase regulation to NOX2 by showing its PLA2 pocket mediates interaction with RAC required for oxidase maturation.

    Evidence Activity-based protein profiling, molecular dynamics, and NOX2 activity assays with the inhibitor Astragaloside IV in an acute lung injury model

    PMID:37030053

    Open questions at the time
    • Direct PRDX6–RAC binding interface not crystallographically resolved
    • Single inhibitor-based mechanistic inference
  11. 2019 High

    Initially attributed PRDX6 ferroptosis suppression to its iPLA2-mediated removal of lipid hydroperoxides.

    Evidence siRNA knockdown/overexpression with erastin/RSL3, LOOH measurement, and MJ33 synergy assays

    PMID:31036877

    Open questions at the time
    • Did not test selenium-dependent contributions to GPX4
    • HO-1 induction mechanism downstream of PRDX6 loss unclear
  12. 2024 High

    Redefined the dominant ferroptosis-protective mechanism, establishing PRDX6 as a selenium-acceptor protein that feeds selenocysteine-tRNA synthesis via SEPHS2 to sustain GPX4, rather than directly reducing PLOOH.

    Evidence Independent biochemical selenium-transfer assays, SEPHS2 interaction, CRISPR knockout, Prdx6-deficient mouse brains, and xenograft ferroptosis assays

    PMID:38867112 PMID:39547222 PMID:39547224

    Open questions at the time
    • Structural basis of selenide handoff to SEPHS2 not resolved
    • Relationship between selenium-acceptor role and the two enzymatic activities unclear
  13. 2020 Medium

    Mapped the transcriptional circuitry controlling PRDX6, showing Bmal1 E-box and Nrf2 ARE cooperate for peak expression and impose circadian regulation.

    Evidence DNA-binding and reporter assays with E-box/ARE mutagenesis and in vivo rhythmic expression in mouse lenses

    PMID:22113199 PMID:29074861 PMID:32784474 PMID:33894270

    Open questions at the time
    • Cross-talk between the activators quantitatively unresolved
    • Tissue-specificity of each element not systematically compared
  14. 2019 Medium

    Identified Klf9 as a direct ARE-induced repressor of PRDX6, explaining how excessive Nrf2 activation can paradoxically lower PRDX6 and promote ROS-driven death and inflammasome activation.

    Evidence Reporter/ChIP assays, Klf9 knockdown/overexpression, promoter mutagenesis, and Prdx6-null inflammasome analysis

    PMID:31569690 PMID:38003466

    Open questions at the time
    • Threshold determinants of activator-vs-repressor balance unclear
    • Single experimental system
  15. 2020 High

    Defined the cellular consequences of complete PRDX6 loss, revealing broad redox-proteome remodeling, mitochondrial dysfunction, cell-cycle arrest, and a metabolic shift to glycolysis.

    Evidence CRISPR knockout in HepG2 with global/redox proteomics, Seahorse, flow cytometry, and electron microscopy

    PMID:33035814

    Open questions at the time
    • Causal cysteine-oxidation targets (e.g., PCNA) not functionally validated
    • Direct vs indirect mitochondrial effects not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PRDX6's three roles—peroxidase, iPLA2, and selenium-acceptor—are coordinated within a single protein and partitioned across cellular compartments and physiological contexts remains unresolved.
  • No integrated structural model linking the catalytic sites to the selenium-acceptor function
  • Compartment-specific deployment of each activity undefined
  • Relative in vivo weight of each function across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0016209 antioxidant activity 3 GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0140104 molecular carrier activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2
Partners
GSTP1JAK2NOXA1NPM1RACSEPHS2
Complex memberships
PRDX6–GSTπ heterodimer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PRDX6 (1-Cys peroxiredoxin) is a bifunctional enzyme with two distinct active sites: Ser32 in the GDSWG motif serves as the catalytic nucleophile for phospholipase A2 (aiPLA2) activity, while Cys47 in the PVCTTE motif is the active site for glutathione peroxidase (NSGPx) activity. Mutation S32A abolishes PLA2 activity without affecting peroxidase; C47S abolishes peroxidase without affecting PLA2. The enzyme exhibits Ca2+-independent PLA2 activity at acidic pH and GSH peroxidase activity at alkaline pH. Site-directed mutagenesis (S32A, C47S), E. coli recombinant expression, in vitro enzymatic assays, inhibitor studies (MJ33, mercaptosuccinate, antibody epitope mapping) The Journal of biological chemistry High 10893423
2004 Activation of 1-Cys peroxiredoxin (PRDX6) requires heterodimerization with pi GST (GSTπ). Oxidized Cys47 in PRDX6 is glutathionylated via GSTπ loaded with GSH, followed by spontaneous reduction of the mixed disulfide, restoring peroxidase activity. Maximum activation occurs at a 1:1 molar ratio of GSH-saturated GSTπ to PRDX6. Partial and homogeneous purification, in vitro heterodimerization assay, liposome-mediated delivery into cells lacking endogenous PRDX6 or GSTπ, biochemical activity assays Proceedings of the National Academy of Sciences of the United States of America High 15004285
2002 Antisense-mediated knockdown of 1-Cys peroxiredoxin (PRDX6) in rat lung epithelial (L2) cells leads to accumulation of phosphatidylcholine hydroperoxides in plasma membranes, lipid peroxidation, and apoptotic cell death (annexin V/PI staining, TUNEL). These effects were rescued by adenoviral overexpression of PRDX6 or vitamin E analogue pretreatment, establishing PRDX6 as a functional antioxidant that prevents phospholipid hydroperoxide accumulation and apoptosis in intact cells. Antisense morpholino oligonucleotide knockdown, immunoblot, HPLC conjugated diene assay, DPPP fluorescence for lipid peroxidation, annexin V/PI staining, TUNEL, adenoviral rescue The Journal of biological chemistry High 12372839
2002 Stable overexpression of GFP-PRDX6 in NCI-H441 lung cells (lacking endogenous PRDX6) reduces H2O2 and t-butylhydroperoxide levels, decreases phosphatidylcholine hydroperoxide accumulation upon oxidant exposure, and protects against oxidant-induced plasma membrane damage (phosphatidylserine translocation) in a GSH-dependent manner. Stable transfection, 51Cr release cytotoxicity assay, TBARS, PCOOH HPLC assay, DPPP fluorescence, Annexin V-Cy3 staining, GSH depletion Proceedings of the National Academy of Sciences of the United States of America High 12193653
2008 H2O2-induced hyperoxidation of PRDX6 Cys47 (to sulfinic acid) is irreversible in vivo (unlike 2-Cys Prxs) and paradoxically increases iPLA2 activity, causing G2/M cell cycle arrest associated with p53/p21 upregulation and cyclin B1 downregulation. C47A mutation abolishes both hyperoxidation and the H2O2-induced iPLA2 upregulation, demonstrating that Cys47 hyperoxidation is required for iPLA2 activation. H2O2 treatment, immunoblot with anti-sulfinic acid antibody, iPLA2 activity assay, site-directed mutagenesis (C47A, S32A, double mutant), cell cycle analysis by flow cytometry, Western blot for p53/p21/cyclin B1 The Journal of biological chemistry High 18826942
2005 PRDX6 uses GSH as electron donor to reduce H2O2 and phospholipid hydroperoxides (rate constant ~3×10^6 M^-1 s^-1). Oxidation of Cys47 to sulfenic acid during catalysis requires piGST-catalyzed glutathionylation and GSH reduction to complete the enzymatic cycle. In vivo, Prdx6-null mice are more sensitive to hyperoxia and paraquat, whereas adenoviral overexpression protects mouse lungs. Kinetic in vitro assays, Prdx6-null mouse model, adenoviral overexpression in mice, hyperoxia and paraquat exposure models Free radical biology & medicine High 15890616
2016 PRDX6 binds to Noxa1 (NADPH oxidase activator 1) via its SH3 domain, stabilizes Noxa1, and supports Nox1-derived superoxide production and cell migration. Both the peroxidase (C47S) and lipase (S32A) mutants of PRDX6 fail to bind or stabilize Nox1 components, and the iPLA2 inhibitor MJ33 suppresses Nox1 activity, implicating the phospholipase activity in Nox1 regulation. Yeast two-hybrid screening, co-IP in overexpressing cells, Nox1 superoxide activity assay, PRDX6 knockdown/overexpression, mutant expression (C47S, S32A), MJ33 pharmacological inhibition, wound-closure migration assay Free radical biology & medicine High 27094494
2015 PRDX6 physically interacts with JAK2 (co-localization and co-immunoprecipitation in tumor tissues and lung cancer cells) and its overexpression activates the JAK2/STAT3 pathway, contributing to urethane-induced lung tumor development in transgenic mice. STAT3 DNA binding and CCL5 levels are also increased. PRDX6 transgenic mice, urethane carcinogenesis model, immunohistochemistry, co-immunoprecipitation, JAK2/STAT3 activity assays, STAT3 DNA binding assay Free radical biology & medicine Medium 25582888
2017 Aberrant SUMO1 conjugation of PRDX6 at Lys122 and Lys142 reduces its cellular abundance and decreases both GSH-peroxidase and aiPLA2 activities. A K122/142R sumoylation-deficient mutant gains enhanced enzymatic activity (30% GPx, 37% aiPLA2 increases) and stability. Phosphorylation at T177 is required for optimal aiPLA2 activity. Both active sites (peroxidase and PLA2) are necessary for mutant PRDX6 function. Site-directed mutagenesis (K122R, K142R, K122/142R, T177A), Prdx6-/- LEC complementation, enzymatic activity assays, stability assays, TAT-fusion protein delivery, EGFP-Sumo1 co-expression Cell death & disease High 28055018
2014 Oxidative stress-induced aberrant SUMO1 conjugation reduces PRDX6 protein abundance and attenuates its transcription. SUMO1 modification of PRDX6 is associated with reduced Sp1 expression and impaired Sp1-mediated transactivation of the Prdx6 promoter. Delivery of SENP1 (SUMO-specific protease) reverses the loss of PRDX6 expression. Immunoblot, Prdx6-/- LECs, Sumo1-fused PRDX6 construct, CAT reporter gene assay, gel mobility shift assay, SENP1 delivery rescue experiments, aging lens analysis The FEBS journal Medium 24910119
2019 PRDX6 knockdown enhances lipid reactive oxygen species (LOOH) and ferroptotic cell death triggered by erastin and RSL-3. This effect correlates with transcriptional activation of heme oxygenase-1 (HO-1), and HO-1 overexpression enhances ferroptosis. The iPLA2 inhibitor MJ33 synergistically enhances erastin-induced ferroptosis, indicating PRDX6 removes LOOH through its iPLA2 activity to protect against ferroptosis. PRDX6 siRNA knockdown, overexpression, ferroptosis inducers (erastin, RSL3), LOOH measurement, HO-1 overexpression, MJ33 iPLA2 pharmacological inhibition, cell death assays Acta pharmacologica Sinica High 31036877
2024 PRDX6 acts as a selenium-acceptor protein and facilitates intracellular selenium utilization by transferring selenium within the selenocysteyl-tRNA[Ser]Sec synthesis machinery, thereby promoting efficient selenoprotein (including GPX4) synthesis. Loss of PRDX6 decreases selenoprotein expression and sensitizes cells to ferroptosis; reduced GPX4 was confirmed in Prdx6-deficient mouse brains. Genetic loss-of-function (PRDX6 knockout/knockdown), selenium transfer biochemistry, selenoprotein expression analysis, Prdx6-/- mouse brains, tumor xenograft ferroptosis sensitivity assays, interaction with SEPHS2 Nature structural & molecular biology High 38867112
2024 PRDX6 acts as a selenium-acceptor protein that can react with selenide and interact with SEPHS2 (selenophosphate synthetase 2), providing an alternative SCLY-independent pathway for selenocysteine (Sec) metabolism and selenoprotein synthesis. This pathway is functionally significant in human cancer cells and is linked to elevated PRDX6 expression in MYCN-amplified neuroblastoma. Biochemical interaction assays (PRDX6 with selenide and SEPHS2), SCLY-independent pathway characterization in human cancer cells, functional complementation assays Molecular cell High 39547224
2024 PRDX6 overexpression alone does not prevent ferroptosis despite its known phospholipid hydroperoxide-reducing activity; however, genetic loss of PRDX6 sensitizes cancer cells to ferroptosis by reducing GPX4 levels (via impaired selenium utilization), not by direct PLOOH reduction. Cells lacking GPX4 retain substantial PLOOH-reducing capacity independent of PRDX6. PRDX6 overexpression and CRISPR knockout in cancer cells, PLOOH measurement, GPX4 expression analysis, Prdx6-deficient mouse brains, tumor xenograft ferroptosis assays Molecular cell High 39547222
2012 The PLA2 activity of PRDX6 mediates its ability to enhance NADPH oxidase (phox) activity in neutrophil-like PLB-985 cells in response to fMLF but not PMA. Knockdown of PRDX6 reduces fMLF-stimulated oxidase activity; reintroduction of wild-type or peroxidase-dead (Prdx active site mutant) PRDX6 restores the response, but PLA2 active site mutants do not. Stable shRNA knockdown in PLB-985 cells, reintroduction of shRNA-resistant WT and mutant (PLA2 and Prdx active site) PRDX6, phox activity assay with fMLF and PMA stimulation European journal of immunology Medium 22678913
2020 CRISPR/Cas9 knockout of PRDX6 in HepG2 hepatocarcinoma cells causes decreased respiratory capacity, downregulation of mitochondrial proteins, altered mitochondrial morphology, G2/M cell cycle arrest, increased ROS, and redox changes at 254 Cys-peptides in 202 proteins. Specific oxidation of cysteines in PCNA may interfere with mitotic entry. The GSH/Glutaredoxin system is downregulated, and cells shift to glycolysis for ATP and AMPK-independent autophagy. CRISPR/Cas9 knockout, quantitative global and redox proteomics, flow cytometry, extracellular flow analysis (Seahorse), Western blot, electron microscopy Redox biology High 33035814
2011 Sp1 directly binds to three active Sp1 sites (-19/27, -61/69, -82/89) in the PRDX6 promoter to transactivate its expression. Curcumin-mediated induction of PRDX6 is dependent on Sp1 activity; point mutations at Sp1 sites abolish curcumin-mediated transactivation. Sp1 inhibitors prevent curcumin-induced PRDX6 upregulation. Bioinformatic analysis, DNA-protein binding assay, co-transfection with Sp1 and Prdx6-CAT constructs, point mutagenesis of Sp1 sites, Sp1 inhibitor treatment, real-time PCR, Western blot Cell death & disease Medium 22113199
2019 At high doses of sulforaphane (>6 μM), excessive Nrf2 activates Klf9 through the ARE site in the Klf9 promoter; Klf9 then directly binds to repressive Klf9 binding elements (RKBE) in the PRDX6 promoter and represses PRDX6 transcription, increasing ROS and causing cell death. Klf9 depletion independently reduces ROS and promotes cell survival. Reporter gene assays, ChIP/DNA binding assays, Klf9 overexpression/ShRNA knockdown, promoter mutagenesis, ROS measurement, cell viability assays Cells Medium 31569690
2020 Bmal1 directly binds E-Box elements in the Prdx6 promoter to regulate its transcription. Both E-Box and ARE (bound by Nrf2) sites are required for peak Prdx6 transcription, and Bmal1/Nrf2/Prdx6 show rhythmic expression in mouse lenses in vivo. Bmal1 depletion disrupts Nrf2 and Prdx6 expression and leads to ROS accumulation. DNA binding assays, transcription assays, promoter mutagenesis (E-Box, ARE), Bmal1 depletion, in vivo circadian expression analysis in mouse lenses Cells Medium 32784474
2017 Nrf2 binds the ARE (-357/-349) in the PRDX6 promoter and drives its transcription; progressive reduction in Nrf2/ARE binding occurs in aging lens epithelial cells, correlating with Prdx6 decline. Mutation at the ARE site prevents sulforaphane-mediated Prdx6 induction. PRDX6 knockdown abolishes sulforaphane-mediated cytoprotection. Gel-shift assay, ChIP assay, promoter-reporter constructs, ARE site mutagenesis, Prdx6 antisense knockdown, UVB stress assays Scientific reports Medium 29074861
2021 Sp1 binds to three Sp1 response elements in the PRDX6 promoter to directly regulate its transcriptional activation in podocytes. Sp1 overexpression upregulates PRDX6 and Sp1 silencing abolishes PRDX6 protective effects against high-glucose-induced podocyte injury. ChIP assay confirming Sp1 binding to Prdx6 promoter, Sp1 overexpression/silencing, PRDX6 overexpression vector, high-glucose podocyte model, streptozotocin DN mouse model Life sciences Medium 33894270
2008 TAT-PRDX6 fusion protein is efficiently transduced into lens epithelial cells from rat and mouse, remains biologically active, reduces ROS, suppresses TGF-β1 activation and cataractogenic markers (α-smooth muscle actin, βig-h3), and delays cataract progression in ex vivo/in vivo models. TAT-protein transduction into primary LECs, immunoblot for ROS and signaling markers, ex vivo lens culture, in vivo cataract progression assessment American journal of physiology. Cell physiology Medium 18184874
2005 Targeted inactivation (knockout) of the Prdx6 gene in lens epithelial cells results in elevated ROS, phenotypic changes indistinguishable from TGFβ-induced cataractogenesis, transcriptional repression of LEDGF, HSP27, and αB-crystallin, and reduced LEDGF binding to stress response elements. PRDX6 supply reverses these changes. Prdx6-/- knockout mice/LECs, biochemical ROS assays, CAT reporter assay, gel mobility shift assay, immunoblot, PRDX6 rescue delivery Cell death and differentiation Medium 15818411
2017 NPM1 (nucleophosmin) co-immunoprecipitates with PRDX6 and regulates its expression; NPM1 knockdown decreases PRDX6 and increases intracellular ROS, while NPM1 overexpression or cytoplasmic localization upregulates PRDX6 and decreases ROS. NSC348884 (NPM oligomerization inhibitor) decreases PRDX6. Co-immunoprecipitation, NPM1 siRNA knockdown and overexpression, ROS measurement by fluorescence, immunoblot for PRDX6/NPM1/ROS markers Journal of cellular biochemistry Low 28513872
2024 PRDX6 iPLA2 activity is involved in astrocyte activation and M1 microglia polarization after ischemic stroke. Blocking iPLA2 activity (by D140A mutation or MJ33) in CTX-TNA2 astrocytes inhibits microglia polarization, reduces ROS production, suppresses NOX2 activation, and inhibits Drp1-dependent mitochondrial fission following OGD/R. MAPKs (ERK, p38) phosphorylate PRDX6 at Thr177 to regulate its iPLA2 activity in astrocytes. PRDX6 D140A and T177A mutations, MJ33 pharmacological inhibition, NOX2 inhibitor (GSK2795039), Drp1 inhibitor (Mdivi-1), ERK/p38 inhibitors (U0126, SB202190), astrocyte-microglia co-culture, OGD/R model, ROS measurement Cell communication and signaling : CCS Medium 38287382
2023 Astragaloside IV (AST) inhibits PRDX6 PLA2 activity by targeting the PLA2 catalytic triad pocket. This binding disrupts the interaction between PRDX6 and RAC (GTPase), hindering RAC-GDI heterodimer activation and NOX2 maturation, thereby attenuating superoxide production. Activity-based protein profiling (ABPP), small molecule-protein interaction assays, molecular dynamics simulation, PLA2 activity assay, NOX2 activity measurement, in vivo acute lung injury model Phytomedicine Medium 37030053
2021 Viral 3C protease (3Cpro) of foot-and-mouth disease virus (FMDV) and Senecavirus A degrades PRDX6 to overcome its antiviral function. PRDX6 overexpression inhibits FMDV replication while knockdown promotes it. The PLA2 activity (inhibited by MJ33) is required for antiviral function; peroxidase inhibition (mercaptosuccinate) does not promote viral replication. 3Cpro-mediated PRDX6 degradation is independent of proteasome, lysosome, and caspase pathways and requires protease activity. PRDX6 overexpression/knockdown, viral replication assay, MJ33 and mercaptosuccinate inhibitors, 3Cpro expression and protease-dead mutant, proteasome/lysosome/caspase inhibitors Virologica Sinica Medium 33721217
2004 Adenovirus-mediated overexpression of 1-Cys peroxiredoxin (PRDX6) in mouse lungs protects against hyperoxic injury, as measured by decreased pleural effusion, lung wet/dry weight, protein and cells in BAL fluid, and reduced TBARS and protein carbonyls. Adenoviral gene transfer in mice, hyperoxia exposure model, BAL fluid analysis, TBARS, protein carbonyl assay, lung wet/dry weight American journal of physiology. Lung cellular and molecular physiology Medium 15136296
2013 Downregulation of PRDX6 by TNF-α and IFN-γ in insulin-producing RINm5F cells is mediated by the calpain and proteasome proteolysis systems and JNK signaling. Blocking JNK, calpains, or the proteasome restores PRDX6 protein levels. IL-4 prevents the cytokine-induced PRDX6 decrease. Cytokine treatment, JNK inhibitor, calpain inhibitor, proteasome inhibitor, PRDX6 siRNA knockdown, Western blot, RT-PCR Molecular and cellular endocrinology Medium 23623867
2022 Prdx6-deficient LECs show augmented NLRP3 inflammasome activation (elevated Caspase-1, IL-1β, ASC, Gasdermin-D) driven by ROS accumulation. Mechanistically, oxidative stress upregulates Klf9, which binds the NLRP3 promoter and increases NLRP3 transcription. Delivery of PRDX6 or silencing of Klf9 prevents the inflammatory response. Prdx6-/- LECs, Klf9 siRNA knockdown, PRDX6 delivery, Nlrp3 promoter assay, immunoblot for inflammasome components, ROS measurement International journal of molecular sciences Medium 38003466
2022 S-palmitoylation at Cys47 of PRDX6 may competitively inhibit disulfide bond formation between Cys47 and Cys91 and alters PRDX6 spatial topology. S-palmitoylation status of Cys47 affects the interaction between PRDX6 and the C-terminal domain of anion exchanger AE3 in dorsal root ganglia, potentially regulating AE3 activity and neuronal excitability. Proteomic comparison of diabetic vs normal mouse DRG, palmitoylome profiling of HUVEC, bioinformatic prediction of palmitoylation sites (Cys47, Cys91), immunofluorescence for PRDX6 subcellular localization Frontiers in endocrinology Low 36120430

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. Free radical biology & medicine 327 15890616
2000 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. The Journal of biological chemistry 285 10893423
2004 Activation of the antioxidant enzyme 1-CYS peroxiredoxin requires glutathionylation mediated by heterodimerization with pi GST. Proceedings of the National Academy of Sciences of the United States of America 276 15004285
2002 1-Cys peroxiredoxin overexpression protects cells against phospholipid peroxidation-mediated membrane damage. Proceedings of the National Academy of Sciences of the United States of America 192 12193653
2017 Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6 activity during aging and oxidative stress. Scientific reports 181 29074861
2021 Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. Life sciences 138 33894270
2019 Identification of PRDX6 as a regulator of ferroptosis. Acta pharmacologica Sinica 124 31036877
2002 An antisense oligonucleotide to 1-cys peroxiredoxin causes lipid peroxidation and apoptosis in lung epithelial cells. The Journal of biological chemistry 107 12372839
2008 TAT-mediated PRDX6 protein transduction protects against eye lens epithelial cell death and delays lens opacity. American journal of physiology. Cell physiology 106 18184874
2008 H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of iPLA2 activity. The Journal of biological chemistry 96 18826942
2005 Impaired homeostasis and phenotypic abnormalities in Prdx6-/-mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFbeta. Cell death and differentiation 84 15818411
2013 Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation. American journal of physiology. Cell physiology 81 23364261
2024 PRDX6 augments selenium utilization to limit iron toxicity and ferroptosis. Nature structural & molecular biology 80 38867112
2020 Clock Protein Bmal1 and Nrf2 Cooperatively Control Aging or Oxidative Response and Redox Homeostasis by Regulating Rhythmic Expression of Prdx6. Cells 80 32784474
2003 Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells. American journal of physiology. Lung cellular and molecular physiology 79 12851211
2021 The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis. Nutrition, metabolism, and cardiovascular diseases : NMCD 77 34953631
2020 Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells. Redox biology 76 33035814
2024 PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization. Molecular cell 72 39547222
2004 Adenovirus-mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury. American journal of physiology. Lung cellular and molecular physiology 71 15136296
2014 PRDX6 promotes lung tumor progression via its GPx and iPLA2 activities. Free radical biology & medicine 67 24512906
2010 Plant thioredoxin CDSP32 regenerates 1-cys methionine sulfoxide reductase B activity through the direct reduction of sulfenic acid. The Journal of biological chemistry 65 20236937
2003 1-Cys peroxiredoxin knock-out mice express mRNA but not protein for a highly related intronless gene. FEBS letters 65 14644414
2024 PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance. Molecular cell 62 39547224
2011 Specificity protein, Sp1-mediated increased expression of Prdx6 as a curcumin-induced antioxidant defense in lens epithelial cells against oxidative stress. Cell death & disease 58 22113199
2017 Prdx6 retards senescence and restores trabecular meshwork cell health by regulating reactive oxygen species. Cell death discovery 52 28904819
2009 PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells. Free radical research 52 19572226
2004 Polyol pathway-dependent osmotic and oxidative stresses in aldose reductase-mediated apoptosis in human lens epithelial cells: role of AOP2. Biochemical and biophysical research communications 52 14751239
2015 PRDX6 promotes tumor development via the JAK2/STAT3 pathway in a urethane-induced lung tumor model. Free radical biology & medicine 51 25582888
2007 Investigating transcriptional regulation of Prdx6 in mouse liver cells. Free radical biology & medicine 50 17382207
2016 Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration. Free radical biology & medicine 49 27094494
2015 PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 49 26279427
2003 Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root. Free radical biology & medicine 48 14572613
2009 Overexpression of Prdx6 and resistance to peroxide-induced death in Hepa1-6 cells: Prdx suppression increases apoptosis. Redox report : communications in free radical research 46 20003713
2015 PRDX6 controls multiple sclerosis by suppressing inflammation and blood brain barrier disruption. Oncotarget 44 26327204
2014 PRDX6 Exacerbates Dopaminergic Neurodegeneration in a MPTP Mouse Model of Parkinson's Disease. Molecular neurobiology 44 25193021
2022 Prdx6-induced inhibition of ferroptosis in epithelial cells contributes to liquiritin-exerted alleviation of colitis. Food & function 42 35983876
1998 Characterization of the murine gene encoding Aop2 (antioxidant protein 2) and identification of two highly related genes. Genomics 42 9806838
2019 Sulforaphane-Induced Klf9/Prdx6 Axis Acts as a Molecular Switch to Control Redox Signaling and Determines Fate of Cells. Cells 40 31569690
2017 Prdx6 Upregulation by Curcumin Attenuates Ischemic Oxidative Damage via SP1 in Rats after Stroke. BioMed research international 39 28596967
2005 Biochemical characterization of Toxoplasma gondii 1-Cys peroxiredoxin 2 with mechanistic similarities to typical 2-Cys Prx. Molecular and biochemical parasitology 39 15694490
2009 Molecular cloning and characterization of 1-Cys and 2-Cys peroxiredoxins from the bumblebee Bombus ignitus. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 38 19932185
2015 Delivery of a protein transduction domain-mediated Prdx6 protein ameliorates oxidative stress-induced injury in human and mouse neuronal cells. American journal of physiology. Cell physiology 37 26447207
2014 Involvement of a 1-Cys peroxiredoxin in bacterial virulence. PLoS pathogens 37 25329795
2001 Bovine eye 1-Cys peroxiredoxin: expression in E. coli and antioxidant properties. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 37 11322641
2024 Analysis of the Expression of PRDX6 in Patients with Hepatocellular Carcinoma and its Effect on the Phenotype of Hepatocellular Carcinoma Cells. Current genomics 36 38544826
2018 Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 36 30562740
2018 PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal. Molecular neurobiology 35 30097850
2006 Identification and characterization of 1-Cys peroxiredoxin from Sulfolobus solfataricus and its involvement in the response to oxidative stress. The FEBS journal 35 16441659
2017 Prdx6 Deficiency Ameliorates DSS Colitis: Relevance of Compensatory Antioxidant Mechanisms. Journal of Crohn's & colitis 34 28199527
2002 Regulation of 1-cys peroxiredoxin expression in lung epithelial cells. American journal of respiratory cell and molecular biology 34 12151315
1999 AOP2 (antioxidant protein 2): structure and function of a unique thiol-specific antioxidant. Antioxidants & redox signaling 34 11233154
2022 PRDX6-mediated pulmonary artery endothelial cell ferroptosis contributes to monocrotaline-induced pulmonary hypertension. Microvascular research 33 36566948
2007 Identification and characterization of a novel 1-Cys peroxiredoxin from silkworm, Bombyx mori. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 33 17933572
2020 Prdx6 Plays a Main Role in the Crosstalk Between Aging and Metabolic Sarcopenia. Antioxidants (Basel, Switzerland) 32 32316601
2013 Modulation of the peroxiredoxin system by cytokines in insulin-producing RINm5F cells: down-regulation of PRDX6 increases susceptibility of beta cells to oxidative stress. Molecular and cellular endocrinology 32 23623867
1999 Characterization of the murine gene encoding 1-Cys peroxiredoxin and identification of highly homologous genes. Gene 32 10395907
2017 Sumoylation-deficient Prdx6 gains protective function by amplifying enzymatic activity and stability and escapes oxidative stress-induced aberrant Sumoylation. Cell death & disease 31 28055018
2014 Characterization of the Vibrio vulnificus 1-Cys peroxiredoxin Prx3 and regulation of its expression by the Fe-S cluster regulator IscR in response to oxidative stress and iron starvation. The Journal of biological chemistry 31 25398878
2018 Overexpression of Peroxiredoxin 6 (PRDX6) Promotes the Aggressive Phenotypes of Esophageal Squamous Cell Carcinoma. Journal of Cancer 29 30410598
2022 Switching of Redox Signaling by Prdx6 Expression Decides Cellular Fate by Hormetic Phenomena Involving Nrf2 and Reactive Oxygen Species. Cells 28 35455944
2022 PRDX6 alleviates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis. Acta odontologica Scandinavica 28 35723029
2020 Overexpression and biological function of PRDX6 in human cervical cancer. Journal of Cancer 28 32201510
2015 Three genes encoding AOP2, a protein involved in aliphatic glucosinolate biosynthesis, are differentially expressed in Brassica rapa. Journal of experimental botany 28 26188204
2013 PRDX1 and PRDX6 are repressed in papillary thyroid carcinomas via BRAF V600E-dependent and -independent mechanisms. International journal of oncology 28 24316730
2014 Aberrant sumoylation signaling evoked by reactive oxygen species impairs protective function of Prdx6 by destabilization and repression of its transcription. The FEBS journal 27 24910119
2008 Conversion of Bacillus subtilis OhrR from a 1-Cys to a 2-Cys peroxide sensor. Journal of bacteriology 26 18586944
2005 Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts. Experimental eye research 26 16360653
2024 PRDX6-iPLA2 aggravates neuroinflammation after ischemic stroke via regulating astrocytes-induced M1 microglia. Cell communication and signaling : CCS 24 38287382
2018 Sumoylation-deficient Prdx6 repairs aberrant Sumoylation-mediated Sp1 dysregulation-dependent Prdx6 repression and cell injury in aging and oxidative stress. Aging 24 30215601
2014 Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxiredoxin 6 (Prdx6) proteins in healthy and pathologic placentas of human and rat. Acta histochemica 24 25171874
2021 miR-24 and its target gene Prdx6 regulate viability and senescence of myogenic progenitors during aging. Aging cell 23 34560818
2015 A 1-Cys Peroxiredoxin from a Thermophilic Archaeon Moonlights as a Molecular Chaperone to Protect Protein and DNA against Stress-Induced Damage. PloS one 23 25933432
2012 Phox activity of differentiated PLB-985 cells is enhanced, in an agonist specific manner, by the PLA2 activity of Prdx6-PLA2. European journal of immunology 23 22678913
2017 Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6. Journal of cellular biochemistry 22 28513872
2016 The role of Prdx6 in the protection of cells of the crystalline lens from oxidative stress induced by UV exposure. Japanese journal of ophthalmology 22 27379999
2009 Age-related cataracts and Prdx6: correlation between severity of lens opacity, age and the level of Prdx 6 expression. The British journal of ophthalmology 21 19429582
2022 Selenocysteine Machinery Primarily Supports TXNRD1 and GPX4 Functions and Together They Are Functionally Linked with SCD and PRDX6. Biomolecules 20 36008942
2015 Lentivirus-mediated inhibition of tumour necrosis factor-α improves motor function associated with PRDX6 in spinal cord contusion rats. Scientific reports 20 25686213
2021 The role of TLR4/NF-κB signaling in the radioprotective effects of exogenous Prdx6. Archives of biochemistry and biophysics 19 33727039
2014 Identification and characterisation of a novel 1-Cys thioredoxin peroxidase gene (AccTpx5) from Apis cerana cerana. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 19 24747012
2015 A novel 1-Cys thioredoxin peroxidase gene in Apis cerana cerana: characterization of AccTpx4 and its role in oxidative stresses. Cell stress & chaperones 18 25971604
2003 Identification of multiple transcripts for antioxidant protein 2 (Aop2): differential regulation by oxidative stress and growth factors. Redox report : communications in free radical research 18 12804011
2023 Astragaloside IV targets PRDX6, inhibits the activation of RAC subunit in NADPH oxidase 2 for oxidative damage. Phytomedicine : international journal of phytotherapy and phytopharmacology 16 37030053
2021 KLF9 regulates PRDX6 expression in hyperglycemia-aggravated bupivacaine neurotoxicity. Molecular and cellular biochemistry 16 33547545
2021 PRDX6 Overexpression Promotes Proliferation, Invasion, and Migration of A549 Cells in vitro and in vivo. Cancer management and research 16 33603470
2015 The Expression of Porcine Prdx6 Gene Is Up-Regulated by C/EBPβ and CREB. PloS one 16 26659441
2006 Biochemical characterization of 1-Cys peroxiredoxin from Antrodia camphorata. Applied microbiology and biotechnology 16 17103164
2024 Glycyrrhetinic acid inhibits non-small cell lung cancer via promotion of Prdx6- and caspase-3-mediated mitochondrial apoptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 38401519
2016 The Antioxidant Peroxiredoxin 6 (Prdx6) Exhibits Different Profiles in the Livers of Seawater- and Fresh Water-Acclimated Milkfish, Chanos chanos, upon Hypothermal Challenge. Frontiers in physiology 15 27965586
2022 NPM1 promotes cell proliferation by targeting PRDX6 in colorectal cancer. The international journal of biochemistry & cell biology 14 35659568
2022 Sp1-Mediated Prdx6 Upregulation Leads to Clasmatodendrosis by Increasing Its aiPLA2 Activity in the CA1 Astrocytes in Chronic Epilepsy Rats. Antioxidants (Basel, Switzerland) 14 36290607
2012 Plasmodium vivax and Plasmodium knowlesi: cloning, expression and functional analysis of 1-Cys peroxiredoxin. Experimental parasitology 14 23178658
2005 Regulation of 1-cys peroxiredoxin expression in the process of stromal wound healing after photorefractive keratectomy. Investigative ophthalmology & visual science 14 15980227
2022 PRDX6: A protein bridging S-palmitoylation and diabetic neuropathy. Frontiers in endocrinology 13 36120430
2021 Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function. Virologica Sinica 13 33721217
2020 Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia. Journal of thrombosis and thrombolysis 13 33047245
2023 Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells. International journal of molecular sciences 12 38003466
2022 Circular RNA hsa_circ_0011385 contributes to cervical cancer progression through sequestering miR-149-5p and increasing PRDX6 expression. Reproductive biology 12 35240453
2015 Anti-cancer effect of snake venom toxin through down regulation of AP-1 mediated PRDX6 expression. Oncotarget 12 26061816
2005 Transcripts associated with Prdx6 (peroxiredoxin 6) and related genes in mouse. Mammalian genome : official journal of the International Mammalian Genome Society 12 15859355

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