Affinage

PRDX2

Peroxiredoxin-2 · UniProt P32119

Round 2 corrected
Length
198 aa
Mass
21.9 kDa
Annotated
2026-04-28
130 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRDX2 is a 2-Cys peroxiredoxin that scavenges hydrogen peroxide with exceptional selectivity and reactivity (~10⁷ M⁻¹ s⁻¹) and transduces H₂O₂ signals to downstream effectors through its unusually long-lived sulfenic acid intermediate (PMID:10873855, PMID:17329258, PMID:30284335). Assembled as a decameric toroid of five homodimers, PRDX2 is recruited to activated PDGF receptor to locally suppress H₂O₂-dependent signaling, and oxidizes STAT3 via a disulfide relay that attenuates STAT3 transcriptional activity, while its glutathionylated form is released from macrophages as an inflammatory danger signal triggering TNF-α production (PMID:15902258, PMID:25402766, PMID:25097261). PRDX2 activity is regulated by Cdk5-mediated Thr89 phosphorylation (inactivating, contributing to neuronal death in Parkinson's disease and ischemia), HDAC6-dependent deacetylation (modulating activity and overoxidation resistance), and peroxynitrite-mediated tyrosine nitration (activating), while overoxidized enzyme is regenerated by the p53-regulated sulfinyl reductase sestrin 2 (PMID:17610816, PMID:18606987, PMID:26612102, PMID:15105503). In erythrocytes, PRDX2 operates as a stoichiometric H₂O₂ scavenger that forms a native complex with catalase, and its oxidized form exhibits molecular chaperone activity that prevents protein aggregation (PMID:17105810, PMID:21354257, PMID:30605715).

Mechanistic history

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

    Determining the atomic structure of PRDX2 revealed how a decameric toroid architecture positions the catalytic Cys51 and requires large conformational rearrangements during catalysis, establishing the structural framework for understanding its peroxidase mechanism.

    Evidence 1.7 Å X-ray crystal structure of human erythrocyte PRDX2 with sedimentation analysis

    PMID:10873855

    Open questions at the time
    • No structure of the reduced active-site form was captured
    • Dynamics of conformational transitions during catalysis unresolved
  2. 2002 High

    Identification of in vivo overoxidation of the active-site cysteine to cysteic acid revealed that irreversible inactivation of PRDX2 modulates susceptibility to TNF-α-induced apoptosis, establishing overoxidation as a functionally consequential event rather than an artifact.

    Evidence 2D-gel proteomics and tandem MS in Leydig cells with apoptosis readout

    PMID:11904290

    Open questions at the time
    • Mechanism linking overoxidized PRDX2 to apoptotic threshold unknown
    • Whether overoxidation gain-of-function (e.g., chaperone) contributes was not tested
  3. 2004 High

    Two discoveries resolved how PRDX2 overoxidation is reversed and what happens in its complete absence in vivo: sestrin 2 was identified as the ATP-dependent sulfinyl reductase that regenerates overoxidized PRDX2, while PRDX2-knockout mice revealed a non-redundant role in thymocyte apoptosis and immune homeostasis through ROS control.

    Evidence In vitro reconstitution with purified sestrin 2; PrxII-knockout mouse with FACS and apoptosis analysis

    PMID:15105503 PMID:15259009

    Open questions at the time
    • Whether other sestrins contribute in specific tissues was not addressed
    • Molecular targets of elevated ROS in PRDX2-null thymocytes unidentified
  4. 2005 High

    Demonstration that PRDX2 is recruited to PDGF receptor and locally eliminates H₂O₂ to suppress receptor signaling established the first paradigm for PRDX2 as a spatially targeted signaling modulator rather than merely a bulk antioxidant.

    Evidence Co-immunoprecipitation of PDGFR-PRDX2, Prdx2-knockout mouse, inactive-mutant control, murine restenosis model

    PMID:15902258

    Open questions at the time
    • How PRDX2 is recruited to PDGFR (adaptor, direct binding domain) uncharacterized
    • Generalizability to other RTKs not tested
  5. 2006 High

    Showing that erythrocyte PRDX2 operates as a stoichiometric H₂O₂ scavenger—exquisitely sensitive to oxidation yet resistant to overoxidation due to limiting thioredoxin reductase—resolved the paradox of how an abundant peroxiredoxin protects cells with negligible catalytic turnover.

    Evidence Non-reducing SDS-PAGE dimerization assay, thioredoxin reductase activity measurement in erythrocyte hemolysates

    PMID:17105810

    Open questions at the time
    • Quantitative contribution of stoichiometric scavenging vs. residual enzymatic turnover not fully delineated
  6. 2007 High

    Two advances defined PRDX2 substrate selectivity and a disease-relevant inactivation mechanism: kinetic measurements established ~10⁷ M⁻¹ s⁻¹ reactivity highly selective for H₂O₂ over other oxidants, while Cdk5-mediated Thr89 phosphorylation was identified as an inactivating modification that promotes dopaminergic neuron death, with elevated pThr89-PRDX2 detected in Parkinson's disease brain tissue.

    Evidence Competition kinetics with HRP; Co-IP of Prx2-Cdk5/p35, T89A/T89E mutagenesis, MPP+/MPTP model, p35-KO neurons, postmortem PD brain immunostaining

    PMID:17329258 PMID:17610816

    Open questions at the time
    • Whether Thr89 phosphorylation occurs in non-neuronal contexts unknown
    • Crystal structure of phospho-PRDX2 not determined
  7. 2008 High

    Identification of HDAC6 as the specific deacetylase of PRDX2 revealed acetylation as a positive regulatory PTM that enhances peroxidase activity and resistance to overoxidation, adding a second layer of post-translational control beyond phosphorylation.

    Evidence HDAC6-knockout/inhibition, in vitro deacetylase assay, H₂O₂ reduction and hyperoxidation assays

    PMID:18606987

    Open questions at the time
    • Identity of the acetyltransferase(s) responsible for PRDX2 acetylation unknown
    • Specific acetylated lysine residues and their individual contributions unresolved
  8. 2009 High

    Extension of the calpain→Cdk5→PRDX2 phosphorylation axis to ischemic stroke models demonstrated that cytoplasmic Cdk5-mediated PRDX2 inactivation is a general mechanism of oxidative neuronal death, not restricted to dopaminergic toxins.

    Evidence Focal and global ischemia mouse models with compartment-specific dominant-negative Cdk5 and Prx2 manipulation

    PMID:19812325

    Open questions at the time
    • Whether other cytoplasmic Cdk5 substrates contribute to ischemic death alongside PRDX2 not dissected
  9. 2011 High

    Native proteomics revealed that erythrocyte PRDX2 exists in multiple oligomeric states including a functional 440 kDa hetero-complex with catalase, and that oxidative stress triggers membrane translocation of oxidized PRDX2, suggesting compartmentalized antioxidant networks.

    Evidence BN-PAGE, 2D-DIGE, size-exclusion chromatography, MS identification, peroxidase activity of isolated complexes

    PMID:21354257

    Open questions at the time
    • Functional significance of membrane-translocated PRDX2 not established
    • Whether the catalase-PRDX2 complex exists in nucleated cells unknown
  10. 2014 High

    Two studies established PRDX2 as a bona fide redox signal transducer: it oxidizes STAT3 via disulfide relay to attenuate STAT3 transcriptional activity, and it is released as glutathionylated PRDX2 from LPS-stimulated macrophages to trigger TNF-α-mediated inflammation, demonstrating both intracellular and extracellular signaling functions.

    Evidence In vitro redox reconstitution of PRDX2-STAT3 relay with reporter assays; MS identification of glutathionylated PRDX2 in macrophage secretome with TNF-α ELISA

    PMID:25097261 PMID:25402766

    Open questions at the time
    • Full set of PRDX2 relay partners beyond STAT3 not mapped
    • Receptor mediating extracellular glutathionylated PRDX2 signaling not identified
  11. 2015 High

    Biophysical analysis showed that peroxynitrite-mediated tyrosine nitration shifts reduced PRDX2 into a conformation resembling the disulfide-oxidized form, mechanistically explaining the observed increase in peroxidase activity upon nitration.

    Evidence Analytical ultracentrifugation, CD, steady-state and time-resolved fluorescence of recombinant PRDX2

    PMID:26612102

    Open questions at the time
    • In vivo relevance of nitrated PRDX2 not demonstrated
    • Specific nitrated tyrosine residues responsible not individually mutated
  12. 2018 High

    The kinetic basis for PRDX2's superior signaling capacity was established: its intramolecular disulfide forms 55-fold slower than PRDX1's (0.2 vs. 11 s⁻¹), prolonging the sulfenic acid intermediate available for mixed-disulfide transfer to signaling partners.

    Evidence In vitro kinetics with recombinant PRDX1 and PRDX2, intrinsic fluorescence monitoring

    PMID:30284335

    Open questions at the time
    • Structural basis for the slow resolution rate not determined
    • Whether the prolonged sulfenic acid reacts with specific partners preferentially not tested
  13. 2019 Medium

    REV7 was identified as a partner that recruits PRDX2 to nuclear DNA double-strand break foci, revealing a previously unrecognized nuclear antioxidant function at DNA damage sites that contributes to radioresistance.

    Evidence Proteomics of REV7 interactors, Co-IP, immunofluorescence co-localization, REV7 knockdown with γH2AX and ROS assays

    PMID:30657231

    Open questions at the time
    • Direct biochemical reconstitution of REV7-PRDX2 interaction not performed
    • Whether PRDX2 peroxidase activity vs. chaperone activity is relevant at DSBs unknown
    • Single lab finding not independently confirmed
  14. 2020 Medium

    Multiple studies positioned PRDX2 as a signaling node upstream of MAPK pathways: PRDX2 depletion activates p38 MAPK/FOXO to arrest cell cycle and induce autophagy in colorectal cancer, while PRDX2 overexpression suppresses p38/JNK/ERK in vascular smooth muscle cells, establishing MAPK suppression as a conserved downstream consequence of PRDX2 activity.

    Evidence shRNA knockdown with p38 activator rescue and xenograft model; overexpression/siRNA with MAPK inhibitor epistasis in VSMCs

    PMID:32692719 PMID:33791345

    Open questions at the time
    • Whether PRDX2 acts on MAPKs through direct H₂O₂ scavenging or specific protein interactions not distinguished
    • Cell-type specificity of MAPK branch preference unexplored
  15. 2022 Medium

    PRDX2 was placed upstream of Akt/mTOR signaling: oxiconazole-induced PRDX2 depletion inactivated Akt/mTOR and caused autophagic arrest, while PRDX2 overexpression rescued, establishing PRDX2 as a regulator of autophagy flux via the Akt/mTOR axis.

    Evidence Drug-induced PRDX2 depletion with overexpression rescue, autophagy flux assays, Akt/mTOR pathway analysis in CRC xenograft

    PMID:35813474

    Open questions at the time
    • Direct molecular link between PRDX2 and Akt activation not identified
    • Whether this involves redox modification of Akt pathway phosphatases unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full repertoire of PRDX2 sulfenic-acid relay partners beyond STAT3, the receptor mediating extracellular glutathionylated PRDX2 inflammatory signaling, the structural basis for PRDX2's slow disulfide resolution that favors signal transmission, and how PRDX2 is spatially recruited to specific signaling complexes (PDGFR, DSB foci).
  • Comprehensive mapping of PRDX2 sulfenic acid interactome not performed
  • No structural model of the PRDX2-STAT3 relay complex
  • Mechanism of PRDX2 recruitment to PDGFR and DNA damage foci undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 6 GO:0016491 oxidoreductase activity 3 GO:0098772 molecular function regulator activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005829 cytosol 4 GO:0005576 extracellular region 1 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 2
Partners
CATCDK5DNMT3AHDAC6MAD2L2PDGFRBSESN2STAT3
Complex memberships
PRDX2 decameric toroid (five homodimers)PRDX2-catalase hetero-oligomeric complex (erythrocyte)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of human decameric peroxiredoxin 2 (TPx-B/PRDX2) from erythrocytes was determined at 1.7 Å resolution, revealing a toroid of five head-to-tail homodimers; the active-site Cys51 was oxidized to cysteine sulphinic acid, trapping a stable decamer, and the structure demonstrated that the catalytic cycle requires significant conformational changes including unwinding of the active-site helix and movement of four loops. X-ray crystallography, sedimentation analysis Structure High 10873855
2002 Proteomics analysis of oxidative stress responses showed that the peroxiredoxin active-site cysteine of PRDX2 is overoxidized in vivo to cysteic acid, inactivating the enzyme; the balance of oxidized vs. native PRDX2 plays an active role in resistance or susceptibility to TNF-α-induced apoptosis in Leydig cells. 2D gel proteomics, tandem mass spectrometry, cell-based apoptosis assays The Journal of biological chemistry High 11904290
2003 PRDX2 is under-expressed in Down syndrome fetal brains; stable antisense knockdown of PRDX2 in SH-SY5Y neuroblastoma cells increased sensitivity to oxidative stress and apoptosis under basal conditions and after oxidative challenge, at levels comparable to the effect of SOD1 overexpression, demonstrating PRDX2's non-redundant role in neuronal redox defense. Suppression subtractive hybridization, real-time PCR, stable antisense transfection, cell viability and apoptosis assays Cellular and molecular life sciences Medium 12943237
2004 Reactive oxygen species elevated by PRDX2 (PrxII) gene deletion in mice led to enlarged thymus with increased thymocyte numbers; PrxII-null thymocytes showed reduced hypodiploid cell formation and resistance to apoptosis induced by dexamethasone or food restriction, establishing PRDX2 as a regulator of thymocyte survival and maturation through ROS control. PrxII knockout mouse model, FACS analysis of thymocyte subsets, apoptosis assays, proliferation assays European journal of immunology High 15259009
2004 Sestrins, whose expression is modulated by p53, are required for regeneration (reduction) of hyperoxidized peroxiredoxins including PRDX2; purified Hi95 (sestrin 2) supports ATP-dependent reduction of overoxidized Prx in vitro, functioning as a cysteine sulfinyl reductase (not a disulfide reductase), thereby reestablishing the antioxidant capacity of PRDX2 after H2O2-mediated overoxidation. In vitro reconstitution with purified proteins, cell-based assays, bioinformatics Science High 15105503
2005 PRDX2 (Prx II) is a negative regulator of PDGF receptor signaling: it is recruited to PDGFR upon PDGF stimulation and locally eliminates H2O2 produced in response to PDGF, thereby suppressing protein tyrosine phosphatase inactivation. PRDX2 deficiency results in enhanced H2O2 production, enhanced PDGFR and PLCγ1 activation, increased VSMC proliferation/migration, and PDGF-dependent neointimal thickening in a murine restenosis model. Prdx2 knockout mouse, co-immunoprecipitation (PDGFR-PRDX2 interaction), cell proliferation/migration assays, murine restenosis model, in vitro peroxidase activity (inactive mutant comparison) Nature High 15902258
2006 PRDX2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in human erythrocytes: it is extremely sensitive to oxidation (dimerization observed at 0.5 µM H2O2), resistant to overoxidation (due to very low thioredoxin reductase activity limiting recycling), and is oxidized by endogenously generated H2O2 from hemoglobin autoxidation, demonstrating its role in erythrocyte defense is stoichiometric rather than enzymatic. H2O2 treatment of erythrocytes, non-reducing SDS-PAGE dimerization assay, thioredoxin reductase activity measurement, hemolysate experiments Blood High 17105810
2007 PRDX2 peroxidase activity is highly selective for H2O2 and organic hydroperoxides (rate constant ~1.3 × 10^7 M^-1 s^-1 for H2O2), but reacts extremely slowly with amino acid chloramines and the alkylating agent iodoacetamide, demonstrating that its tertiary structure facilitates H2O2 reactivity while restricting reactivity with other thiol reagents. Competition kinetics with horseradish peroxidase, non-reducing SDS-PAGE dimerization inhibition assay, multiple oxidant comparisons The Journal of biological chemistry High 17329258
2007 PRDX2 (Prx2) is phosphorylated at Thr89 by Cdk5/p35 in neurons treated with MPP+/MPTP; this phosphorylation reduces Prx2 peroxidase activity. Calpain-mediated Cdk5 activation upstream drives this modification. Expression of phosphorylation-resistant Prx2T89A (but not the phosphomimetic Prx2T89E) protects dopaminergic neurons from mitochondrial toxin-induced death, and Prx2 Thr89 phosphorylation is elevated in nigral neurons of Parkinson's disease patients. Co-immunoprecipitation (Prx2-Cdk5/p35), site-directed mutagenesis (T89A, T89E), in vitro peroxidase activity assay, MPP+/MPTP neurotoxicity model, p35 knockout neurons, transgenic overexpression, postmortem human brain immunostaining Neuron High 17610816
2008 HDAC6 is a specific deacetylase of PRDX2 (and PRDX1); acetylation of PRDX2 (accumulating when HDAC6 is inactive) increases its H2O2-reducing activity, its resistance to superoxidation, and its resistance to transition to high-molecular-mass complexes, identifying acetylation as a positive regulatory PTM for PRDX2 enzymatic function. HDAC6 knockout/inhibition, immunoprecipitation, in vitro deacetylase assay, H2O2 reduction activity assay, hyperoxidation resistance assay Proceedings of the National Academy of Sciences of the United States of America High 18606987
2009 Cytoplasmic Cdk5 is critically activated in stroke models (focal and global ischemia) in vivo, and PRDX2 (Prx2) is a critical cytoplasmic target of Cdk5; expression of dominant-negative Cdk5 localized to the cytoplasm is neuroprotective, and manipulation of Prx2 modulates neuronal survival after ischemic insult, establishing the calpain→Cdk5→Prx2 phosphorylation axis in ischemic neuronal death. Focal and global stroke mouse models, compartment-specific dominant-negative Cdk5 constructs, subcellular fractionation, Prx2 manipulation, neuronal death quantification The Journal of neuroscience High 19812325
2011 In human erythrocytes, PRDX2 (PrxII) exists in four distinct oligomeric states in the cytosol: a 440 kDa hetero-oligomeric complex with tetrameric catalase, and homo-polymeric complexes at 140, 100, and 67 kDa. Under oxidative stress (28-day storage), the 100 kDa complex disappears, the catalase-PrxII complex shifts to 480 kDa (incorporating cross-linked hemoglobin), and oxidized PrxII translocates to the membrane. Peroxidase activity was demonstrated for the 440 kDa and 140 kDa oligomers. Native proteomics (2D-DIGE, BN-PAGE), mass spectrometry, size-exclusion chromatography, peroxidase activity assay, fractionation of cytosol vs. membrane Biochimie High 21354257
2014 PRDX2 forms a redox relay with transcription factor STAT3: PRDX2 acts as an H2O2 signal receptor (reacting at ~10^7–10^8 M^-1 s^-1) and transmitter, oxidizing STAT3 via disulfide exchange to generate disulfide-linked STAT3 oligomers with attenuated transcriptional activity. Cytokine-induced STAT3 signaling is accompanied by co-oxidation of PRDX2 and STAT3, and is modulated by PRDX2 expression levels. Co-immunoprecipitation, non-reducing SDS-PAGE, in vitro redox reconstitution, siRNA knockdown/overexpression, cytokine stimulation, reporter assays Nature chemical biology High 25402766
2014 Inflammatory stimuli (LPS) induce release of glutathionylated PRDX2 from macrophages; extracellular glutathionylated PRDX2 acts as a redox-dependent danger signal triggering macrophages to produce TNF-α. PRDX2 is constitutively present intracellularly in reduced form and is released in oxidized (glutathionylated) form upon LPS stimulation. Co-released thioredoxin enables an oxidative cascade modifying surface receptor -SH groups to facilitate inflammatory activation. Mass spectrometry proteomic identification of glutathionylated proteins in LPS-stimulated macrophage conditioned medium, ELISA for TNF-α, Western blot, LPS stimulation of multiple cell types Proceedings of the National Academy of Sciences of the United States of America High 25097261
2015 Peroxynitrite-mediated nitration of PRDX2 on non-catalytic tyrosines causes the reduced nitrated enzyme to adopt a conformation resembling the disulfide-oxidized native form, facilitating disulfide bond formation; this structural change explains the previously observed increase in peroxidase activity and resistance to overoxidation of nitrated PRDX2. Analytical ultracentrifugation, UV absorption, circular dichroism, steady-state and time-resolved fluorescence of recombinant human PRDX2 Archives of biochemistry and biophysics High 26612102
2018 Among interphase CDKs, CDK2 is specifically degraded via ubiquitin-proteasome pathway (with KLHL6 as E3 ligase) during AML differentiation; CDK2 depletion reactivates the differentiation pathway in part by reducing its direct maintenance of PRDX2 activity. The CDK2-PRDX2 axis maintains the differentiation block in AML cells. Yeast 2-hybrid (CDK2-KLHL6 interaction), ubiquitination assays, CDK2 inhibition/knockdown, AML differentiation assays (cell lines and primary patient samples), PRDX2 activity measurement, xenograft mouse models Blood Medium 29720484
2018 Kinetic analysis shows that PRDX2 (unlike PRDX1) has a slow rate of intramolecular disulfide formation during catalytic cycle (0.2 s^-1 vs 11 s^-1 for PRDX1), creating a longer-lived sulfenic acid intermediate; this kinetic pause allows PRDX2's peroxidatic cysteine sulfenic acid to react with other protein thiols to transmit redox signals via mixed disulfides, differentiating its signaling role from PRDX1. In vitro kinetics using recombinant human PRDX1 and PRDX2, intrinsic fluorescence monitoring of oxidation and hyperoxidation with H2O2 and peroxynitrite Protein science High 30284335
2018 Radioprotective effects of exogenous recombinant PRDX2 in X-ray-irradiated animals are mediated by its peroxidase activity, its chaperone activity in the oxidized state (preventing protein misfolding and aggregation), and signal-regulatory functions via H2O2 level modulation; exogenous PRDX2 reduces ROS, suppresses apoptosis, prevents leukopenia/thrombocytopenia, and protects bone marrow DNA. Whole-body X-ray irradiation in vivo model, recombinant PRDX2 administration, survival studies, ROS measurement, apoptosis assays, bone marrow DNA damage assays Free radical biology & medicine Medium 30605715
2018 DNMT3A-R882H/C mutations in AML upregulate PRDX2 expression through promoter hypomethylation; elevated PRDX2 decreases ROS accumulation and reduces apoptosis, promoting leukemogenesis. Both DNMT3A-WT and R882H/C mutants physically interact with PRDX2. Knockdown of PRDX2 from DNMT3A-mutant myeloid cells restores drug sensitivity and apoptosis. Co-immunoprecipitation (DNMT3A-PRDX2 interaction), DNA methylation assay, gene expression profiling, PRDX2 knockdown, ROS measurement, apoptosis assays Neoplasia Medium 30245403
2019 REV7, the structural subunit of DNA polymerase ζ, interacts with PRDX2 and recruits it to nuclear foci at DNA double-strand breaks post-irradiation; REV7 knockdown disrupts nuclear PRDX2 localization, causing increased oxidative stress and unrepaired DSBs, establishing a REV7-PRDX2 complex that confers radioresistance by protecting against oxidative stress at DSBs. Proteomic analysis of REV7-interacting proteins, co-immunoprecipitation, immunofluorescence co-localization, REV7 knockdown/overexpression, ROS measurement, γH2AX (DSB) assay, xenograft model Cancer science Medium 30657231
2019 H. pylori infection activates NF-κB which transcriptionally upregulates PRDX2 (NF-κB-p65 binding site on PRDX2 promoter confirmed by luciferase reporter and ChIP assays); PRDX2 knockdown in gastric cancer cells increases ROS, oxidative DNA damage, and double-strand breaks in response to H. pylori, and sensitizes cells to cisplatin treatment. Luciferase reporter assay, ChIP assay, PRDX2 knockdown (shRNA), H2DCFDA ROS assay, 8-oxoguanine, γH2AX, in vitro and in vivo H. pylori infection models Redox biology High 31536951
2020 PRDX2 removal in colorectal cancer cells by shRNA inhibits S-phase progression and induces autophagy via the p38 MAPK/FOXO signaling pathway; the p38 activator dehydrocorydaline partially rescues cell-cycle and autophagy effects of PRDX2 knockdown, placing PRDX2 upstream of p38 MAPK in cell-cycle control. shRNA knockdown, flow cytometry (cell cycle), electron microscopy (autophagy), Western blot (p38 activation), immunostaining, p38 activator rescue, xenograft mouse model Aging Medium 32692719
2020 PRDX2 overexpression in H9c2 cardiomyocytes promotes TLR4-mediated inflammatory factor expression (IL-1β, TNF-α, IL-6) and VEGF expression under hypoxia while inhibiting ROS-mediated injury, demonstrating a dual role: cytoprotective (ROS scavenging) and pro-inflammatory (via TLR4 pathway activation). PRDX2 overexpression in H9c2 cells, AMI mouse model, ELISA, immunocytochemistry, immunofluorescence, ROS measurement Scientific reports Medium 28765537
2020 PRDX2 inhibits TLR4/NF-κB signaling in myocardial cells after acute myocardial infarction: recombinant PRDX2 treatment in AMI rats decreases ROS, reduces caspase-family expression, inhibits p65 phosphorylation, and suppresses TLR4/NF-κB pathway activity, reducing myocardial apoptosis. AMI rat model (LAD ligation), recombinant PRDX2 administration, Western blot, qRT-PCR, ROS assay Medical science monitor Medium 33268762
2021 CircDIDO1 specifically binds PRDX2 protein and promotes RBX1-mediated ubiquitination and proteasomal degradation of PRDX2, leading to inactivation of PRDX2 downstream signaling pathways; this reduces gastric cancer cell proliferation, migration, and invasion. Tagged RNA affinity purification, mass spectrometry, co-immunoprecipitation, immunofluorescence, Western blot, gain/loss-of-function studies, xenograft mouse models Molecular cancer Medium 34384442
2021 PRDX2 overexpression in vascular smooth muscle cells reduces ROS (H2O2), collagen I/III, VCAM-1, and ICAM-1 expression, and inhibits VSMC proliferation, migration, and phenotype transformation; PRDX2 suppresses p-p38, p-JNK, and p-ERK activation (MAPK pathway), providing protection against atherosclerosis. MAPK inhibitor treatment confirmed the mechanistic link. PRDX2 overexpression/siRNA knockdown in CAVSMCs, MAPK inhibitors (SB203580, SP600125, PD98059), proliferation/migration assays, Western blot, immunostaining Frontiers in cardiovascular medicine Medium 33791345
2022 Oxiconazole downregulates PRDX2 protein levels to initiate autophagy in colorectal cancer cells by inactivating the Akt/mTOR pathway and inhibiting RAB7A-mediated autophagosome-lysosome fusion, causing extreme accumulation of autophagosomes; PRDX2 overexpression rescues OXI-induced autophagy arrest, establishing PRDX2 as a critical node upstream of Akt/mTOR in autophagy regulation. Drug treatment, PRDX2 overexpression rescue, autophagy flux assays, Akt/mTOR pathway Western blot, RAB7A analysis, CRC xenograft model International journal of biological sciences Medium 35813474
2023 Dihydromyricetin (DHM) induces neuroprotection after subarachnoid hemorrhage through a Nrf2-dependent increase in PRDX2 expression that decreases phosphorylation of p38 and ASK1; siRNA knockdown of Prx2 or Nrf2 inhibition with ML385 attenuates DHM's neuroprotective effects, placing PRDX2 downstream of Nrf2 in the anti-oxidative cascade triggered by DHM. SAH rat model, siRNA knockdown of Prx2, Nrf2 inhibitor ML385, neurological behavioral tests, ROS assay, Western blot, immunofluorescence, primary cortical neurons in vitro Phytomedicine Medium 37523836

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
1996 Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. The EMBO journal 746 8635458
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science (New York, N.Y.) 625 15105503
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2014 Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nature chemical biology 495 25402766
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2000 Identification of a new type of mammalian peroxiredoxin that forms an intramolecular disulfide as a reaction intermediate. The Journal of biological chemistry 385 10751410
2002 Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science (New York, N.Y.) 383 12386337
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2002 Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site. The Journal of biological chemistry 327 11904290
2005 Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature 325 15902258
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2007 The high reactivity of peroxiredoxin 2 with H(2)O(2) is not reflected in its reaction with other oxidants and thiol reagents. The Journal of biological chemistry 311 17329258
2014 Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal. Proceedings of the National Academy of Sciences of the United States of America 282 25097261
2008 HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proceedings of the National Academy of Sciences of the United States of America 282 18606987
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2000 Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 A resolution. Structure (London, England : 1993) 268 10873855
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2012 Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free radical biology & medicine 236 22902630
2006 Peroxiredoxin 2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in the erythrocyte. Blood 232 17105810
2003 Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders. Brain research 232 12650976
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
2007 Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron 216 17610816
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2002 Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation. The Journal of biological chemistry 207 11986303
1998 Prx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs. Development (Cambridge, England) 204 9729491
2012 Growth factor content in PRP and their applicability in medicine. Journal of biological regulators and homeostatic agents 184 23648195
1997 RNA aptamers specifically interact with the prion protein PrP. Journal of virology 175 9343239
1997 PrP genetics in sheep and the applications for scrapie and BSE. Trends in microbiology 163 9263413
2021 CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability. Molecular cancer 134 34384442
2000 Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. Journal of molecular biology 131 10903871
2003 Trafficking, turnover and membrane topology of PrP. British medical bulletin 116 14522850
2003 PrP knock-out and PrP transgenic mice in prion research. British medical bulletin 113 14522848
2019 Review of concentration yields in commercially available platelet-rich plasma (PRP) systems: a call for PRP standardization. Regional anesthesia and pain medicine 104 30992411
1995 Prion protein (PrP) synthetic peptides induce cellular PrP to acquire properties of the scrapie isoform. Proceedings of the National Academy of Sciences of the United States of America 104 7479957
2019 PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer. Redox biology 95 31536951
1992 Diversity of immunodominant 56-kDa type-specific antigen (TSA) of Rickettsia tsutsugamushi. Sequence and comparative analyses of the genes encoding TSA homologues from four antigenic variants. The Journal of biological chemistry 95 1618776
2018 Ubiquitin-dependent degradation of CDK2 drives the therapeutic differentiation of AML by targeting PRDX2. Blood 84 29720484
2013 The pH-triggered conversion of the PrP(c) to PrP(sc.). Current topics in medicinal chemistry 81 23647538
2017 Histone deacetylase inhibitors VPA and TSA induce apoptosis and autophagy in pancreatic cancer cells. Cellular oncology (Dordrecht, Netherlands) 80 28160167
2021 Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE) Study. Journal for immunotherapy of cancer 77 34266881
2018 Genetic PrP Prion Diseases. Cold Spring Harbor perspectives in biology 77 28778873
2013 Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes. World journal of plastic surgery 72 25489498
2000 Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus. Virchows Archiv : an international journal of pathology 72 10664157
2015 Protein-ligand interactions investigated by thermal shift assays (TSA) and dual polarization interferometry (DPI). Acta crystallographica. Section D, Biological crystallography 70 25615858
2012 PK-sensitive PrP is infectious and shares basic structural features with PK-resistant PrP. PLoS pathogens 70 22396643
2012 The N-terminal, polybasic region of PrP(C) dictates the efficiency of prion propagation by binding to PrP(Sc). The Journal of neuroscience : the official journal of the Society for Neuroscience 64 22745483
2020 Tyramide signal amplification mass spectrometry (TSA-MS) ratio identifies nuclear speckle proteins. The Journal of cell biology 63 32609799
2009 Essential role of cytoplasmic cdk5 and Prx2 in multiple ischemic injury models, in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 19812325
2018 The Structure of PrPSc Prions. Pathogens (Basel, Switzerland) 62 29414853
2004 Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant PrP formation. The Journal of general virology 62 15483265
2019 Role of Cytosolic 2-Cys Prx1 and Prx2 in Redox Signaling. Antioxidants (Basel, Switzerland) 57 31185618
2008 Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP. Journal of neurochemistry 57 18691383
2002 Genomic characterization of the human prion protein (PrP) gene locus. Mammalian genome : official journal of the International Mammalian Genome Society 57 12514748
2001 The identification of Prx1 transcription regulatory domains provides a mechanism for unequal compensation by the Prx1 and Prx2 loci. The Journal of biological chemistry 55 11373278
2014 The GPI-anchoring of PrP: implications in sorting and pathogenesis. Prion 54 24509692
2008 Progress and limits of PrP gene selection policy. Veterinary research 54 18258168
2003 Putative functions of PrP(C). British medical bulletin 50 14522849
2005 PrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line. Biochemical and biophysical research communications 49 15670743
2003 Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, is under-expressed in Down syndrome fetal brains. Cellular and molecular life sciences : CMLS 48 12943237
2021 An update on platelet-rich plasma (PRP) therapy in endometrium and ovary related infertilities: clinical and molecular aspects. Systems biology in reproductive medicine 44 33632047
2019 Platelet-Rich Plasma (PRP) From Older Males With Knee Osteoarthritis Depresses Chondrocyte Metabolism and Upregulates Inflammation. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 44 31042308
2004 Reactive oxygen species induced by the deletion of peroxiredoxin II (PrxII) increases the number of thymocytes resulting in the enlargement of PrxII-null thymus. European journal of immunology 42 15259009
2018 Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2. Protein science : a publication of the Protein Society 41 30284335
2020 Peroxiredoxin2 (Prdx2) Reduces Oxidative Stress and Apoptosis of Myocardial Cells Induced by Acute Myocardial Infarction by Inhibiting the TLR4/Nuclear Factor kappa B (NF-κB) Signaling Pathway. Medical science monitor : international medical journal of experimental and clinical research 38 33268762
2011 Oxidative stress-dependent oligomeric status of erythrocyte peroxiredoxin II (PrxII) during storage under standard blood banking conditions. Biochimie 38 21354257
2017 Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the PI3K/AKT signaling pathway. Bioscience reports 37 28432271
2001 Identification of domains mediating transcription activation, repression, and inhibition in the paired-related homeobox protein, Prx2 (S8). DNA and cell biology 36 11244566
2018 Protective and adaptogenic role of peroxiredoxin 2 (Prx2) in neutralization of oxidative stress induced by ionizing radiation. Free radical biology & medicine 35 30605715
2002 The PrP-like protein Doppel binds copper. The Journal of biological chemistry 35 12482851
2004 The role of PrP in health and disease. Current molecular medicine 34 15354865
2019 REV7 confers radioresistance of esophagus squamous cell carcinoma by recruiting PRDX2. Cancer science 33 30657231
2019 Transition of the prion protein from a structured cellular form (PrPC ) to the infectious scrapie agent (PrPSc ). Protein science : a publication of the Protein Society 33 31583788
2010 A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines. PloS one 33 20339552
2008 TSA downregulates Wilms tumor gene 1 (Wt1) expression at multiple levels. Nucleic acids research 33 18535006
2015 Traditional serrated adenoma (TSA): morphological questions, queries and quandaries. Journal of clinical pathology 32 26553935
2006 Three in one: TSA, TSA', and SA units in one crystal structure of a yttrium(III) complex with a monophosphinated H4dota analogue. Inorganic chemistry 31 16562966
2011 The PrP-like proteins Shadoo and Doppel. Topics in current chemistry 29 21728138
2009 Prx1 and Prx2 cooperatively regulate the morphogenesis of the medial region of the mandibular process. Developmental dynamics : an official publication of the American Association of Anatomists 29 19777594
2008 Structure, organization and expression of common carp (Cyprinus carpio L.) NKEF-B gene. Fish & shellfish immunology 29 19032984
2017 Effects of platelet rich plasma (PRP) on human gingival fibroblast, osteoblast and periodontal ligament cell behaviour. BMC oral health 27 28578703
2014 PrP overdrive: does inhibition of α-cleavage contribute to PrP(C) toxicity and prion disease? Prion 26 24721836
2024 Implications and progression of peroxiredoxin 2 (PRDX2) in various human diseases. Pathology, research and practice 25 38219498
2018 Genetic and Epigenetic Perturbations by DNMT3A-R882 Mutants Impaired Apoptosis through Augmentation of PRDX2 in Myeloid Leukemia Cells. Neoplasia (New York, N.Y.) 25 30245403
2020 STVNa Attenuates Isoproterenol-Induced Cardiac Hypertrophy Response through the HDAC4 and Prdx2/ROS/Trx1 Pathways. International journal of molecular sciences 24 31968660
2017 Experimental Models of Inherited PrP Prion Diseases. Cold Spring Harbor perspectives in medicine 24 28096244
2015 Functional and structural changes in plant mitochondrial PrxII F caused by NO. Journal of proteomics 24 25682994
2009 Design and delivery of a cryptic PrP(C) epitope for induction of PrP(Sc)-specific antibody responses. Vaccine 24 19925901
1997 Characterization of a prion protein (PrP) gene from rabbit; a species with apparent resistance to infection by prions. Gene 24 9031631
1995 Preparation and characterization of antibodies against mouse prion protein (PrP) peptides. Clinical and diagnostic laboratory immunology 24 7535178
2020 PRDX2 removal inhibits the cell cycle and autophagy in colorectal cancer cells. Aging 23 32692719
2017 PRDX2 in Myocyte Hypertrophy and Survival is Mediated by TLR4 in Acute Infarcted Myocardium. Scientific reports 23 28765537
1995 A candidate marsupial PrP gene reveals two domains conserved in mammalian PrP proteins. Gene 23 7622046
2023 EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression. International journal of molecular sciences 22 37446194
2021 Platelet HMGB1 in Platelet-Rich Plasma (PRP) promotes tendon wound healing. PloS one 22 34529657
2020 Goats naturally devoid of PrPC are resistant to scrapie. Veterinary research 22 31924264
2020 PRDX2 plays an oncogenic role in esophageal squamous cell carcinoma via Wnt/β-catenin and AKT pathways. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 22 32130676
2020 Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis. Cancer research and treatment 22 33017884
2014 Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues. International journal of oncology 21 25339198
2018 Global analysis of erythroid cells redox status reveals the involvement of Prdx1 and Prdx2 in the severity of beta thalassemia. PloS one 20 30521599
2013 The ZIP5 ectodomain co-localizes with PrP and may acquire a PrP-like fold that assembles into a dimer. PloS one 20 24039764
2012 Unraveling the neuroprotective mechanisms of PrP (C) in excitotoxicity. Prion 20 22437735
2002 Do ambulatory-use Platelet-Rich Plasma (PRP) concentrates present risks? Medicina oral : organo oficial de la Sociedad Espanola de Medicina Oral y de la Academia Iberoamericana de Patologia y Medicina Bucal 20 12415222
2022 Repurposing Oxiconazole against Colorectal Cancer via PRDX2-mediated Autophagy Arrest. International journal of biological sciences 19 35813474
2020 What is the potential use of platelet-rich-plasma (PRP) in cancer treatment? A mini review. Heliyon 19 32258495
2019 PMCA-replicated PrPD in urine of vCJD patients maintains infectivity and strain characteristics of brain PrPD: Transmission study. Scientific reports 19 30914754
2017 PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection. Journal of virology 19 27847358
2007 Prion protein (PrP) in human teeth: an unprecedented pointer to PrP's function. Journal of endodontics 19 17258625
2019 Autologous Platelet-Rich Plasma (CuteCell PRP) Safely Boosts In Vitro Human Fibroblast Expansion. Tissue engineering. Part A 18 30896295
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2023 Dihydromyricetin confers cerebroprotection against subarachnoid hemorrhage via the Nrf2-dependent Prx2 signaling cascade. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 37523836
2017 Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils. Chemical science 17 28989689
2013 PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease. PloS one 17 23922744
2021 PRDX2 Protects Against Atherosclerosis by Regulating the Phenotype and Function of the Vascular Smooth Muscle Cell. Frontiers in cardiovascular medicine 16 33791345
2019 Prdx2 Upregulation Promotes the Growth and Survival of Gastric Cancer Cells. Pathology oncology research : POR 16 31807984
2014 Regulation of PrP(C) signaling and processing by dimerization. Frontiers in cell and developmental biology 16 25364762
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2015 Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin 2; nitrated Prx2 resembles its disulfide-oxidized form. Archives of biochemistry and biophysics 15 26612102
2007 A monoclonal antibody (1D12) defines novel distribution patterns of prion protein (PrP) as granules in nucleus. Biochemical and biophysical research communications 15 18068119
2019 Effects of PRP and LyPRP on osteogenic differentiation of MSCs. Journal of biomedical materials research. Part A 14 31498962
2015 Mammalian prion protein (PrP) forms conformationally different amyloid intracellular aggregates in bacteria. Microbial cell factories 14 26536866
2002 Comparative analysis of Prx1 and Prx2 expression in mice provides evidence for incomplete compensation. The Anatomical record 14 11748565