Affinage

GPX2

Glutathione peroxidase 2 · UniProt P18283

Length
190 aa
Mass
22.0 kDa
Annotated
2026-06-10
66 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPX2 (GSHPx-GI) is a cytosolic, tetrameric selenium-dependent glutathione peroxidase that reduces H2O2 and organic hydroperoxides — but not phosphatidylcholine hydroperoxide — using glutathione as electron donor, defining it as a distinct member of the selenium-dependent GPX family (PMID:8428933). In the intestine, GPX2 acts together with GPX1 as the major glutathione peroxidase activity that maintains mucosal homeostasis: combined Gpx1/Gpx2 loss produces inflammatory ileocolitis that progresses to adenocarcinoma in a manner dependent on commensal bacteria and on Duox2-generated ROS (PMID:11518697, PMID:14871826, PMID:27930931), while GPX2 loss alone increases crypt-base apoptosis, expands the proliferative zone, and shifts epithelial differentiation commitment (PMID:20828612, PMID:29416634). GPX2 suppresses pro-inflammatory PGE2 production by compartmentalized hydroperoxide removal, co-localizing with COX-2 and restraining COX-2/mPGES-1 induction (PMID:18479189). Its expression is driven by multiple regulatory inputs: the Wnt β-catenin/TCF complex (PMID:17937616, PMID:22683372), p63 (but not p53) (PMID:16446369), IL-22/STAT3 (PMID:26115075), and NRF2 downstream of a CBX3/CUL3 axis (PMID:40089640); post-transcriptionally GPX2 mRNA is stabilized by PCBP2 (PMID:35798180), destabilized by METTL14-dependent m6A modification (PMID:40533443) and repressed by miR-185 (PMID:23934683), while its protein is stabilized by the deubiquitinases USP15 (at K187, recruited by ACVRL1) and USP10 (PMID:37743483, PMID:42133228). Through ROS scavenging, GPX2 sustains tumor-initiating and cancer-stem-cell capacity, differentiation, and metastasis, acting upstream of ROS to protect against oxidative-stress-induced apoptosis (PMID:16446369, PMID:25261240, PMID:36725188) and to activate pro-tumorigenic signaling including PI3K/AKT/mTOR/Snail and Hedgehog/GLI (PMID:37287867, PMID:40533443). In endoderm development, GPX2 is a gatekeeper of posterior foregut fate, controlling oxidative-stress levels that regulate BMP signaling and bias differentiation toward the pancreatic over hepatic lineage (PMID:41484137).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 High

    Established GPX2 as a biochemically distinct, selenium-dependent glutathione peroxidase, answering whether the gastrointestinal GPX activity was a separate enzyme from GPX1/plasma GPX.

    Evidence cDNA expression in MCF-7 cells, 75Se-labeling, substrate-specificity enzyme assays, and immunological cross-reactivity testing

    PMID:8428933

    Open questions at the time
    • No structural model of the tetramer or catalytic selenocysteine site provided
    • Physiological substrate range in vivo not resolved beyond in vitro assays
  2. 2004 High

    Genetic loss-of-function defined GPX2's physiological role in intestinal homeostasis and showed that its deficiency drives carcinogenesis only in the presence of inflammation-inducing commensal bacteria.

    Evidence Gpx1/Gpx2 double-knockout and germ-free/colonized mouse models with histopathology and lipid hydroperoxide/myeloperoxidase readouts

    PMID:11518697 PMID:14871826

    Open questions at the time
    • Redundancy with GPX1 obscures GPX2-specific requirement
    • Bacterial species/host signaling linking dysbiosis to tumor initiation not defined
  3. 2010 High

    Single-gene GPX2 knockout revealed a cell-autonomous role in restraining crypt-base apoptosis and proliferation, and uncovered compensatory post-translational upregulation of GPX1.

    Evidence GPX2 knockout mice with crypt apoptosis/mitosis quantification and GPX1 protein vs mRNA analysis

    PMID:20828612

    Open questions at the time
    • Mechanism of post-translational GPX1 compensation unknown
    • Whether apoptosis is purely ROS-driven not established here
  4. 2008 High

    Linked GPX2 to inflammatory signaling by showing it suppresses COX-2/mPGES-1-driven PGE2 production through compartmentalized hydroperoxide removal at the ER.

    Evidence siRNA knockdown in HT-29 cells with COX-2/mPGES-1 Western blot, PGE2 ELISA, and GPX2/COX-2 co-localization

    PMID:18479189

    Open questions at the time
    • Direct hydroperoxide substrate controlling COX-2 induction not identified
    • Cytosolic enzyme localizing to ER compartment mechanistically unexplained
  5. 2012 High

    Mapped the transcriptional and post-translational control of GPX2, establishing Wnt/β-catenin as a direct driver in crypts and p63/STAT3 as additional inputs.

    Evidence Promoter mutagenesis/reporter assays, ChIP, β-catenin and APC manipulation, inducible β-catenin knockout, and IL-22/STAT cotransfection across cell and mouse models

    PMID:16446369 PMID:17937616 PMID:22683372 PMID:26115075

    Open questions at the time
    • Integration of competing transcriptional inputs in a single cell context not resolved
    • p53-dependence of GPX2's cytoprotection mechanistically unexplained
  6. 2014 High

    Placed GPX2 upstream of ROS in maintaining tumor-initiating capacity, demonstrating that ROS scavenging is the operative mechanism through a ROS-neutralization rescue.

    Evidence GPX2 silencing/overexpression in colorectal colonosphere cultures with ROS measurement, clonogenic/metastasis assays, and ROS neutralization rescue

    PMID:25261240

    Open questions at the time
    • Downstream redox-sensitive effectors of clonogenicity not identified here
    • Patient-derived culture results not tied to a specific signaling axis
  7. 2017 High

    Extended GPX2 regulation to YAP/p63 and demonstrated developmental and differentiation roles, showing GPX2 controls intestinal cell-fate marker expression and endoderm lineage choice.

    Evidence Small-molecule/PDX studies of the YAP-p63-GPX2 axis, proteomic profiling of GPX2 KO colon, and hPSC differentiation with chromatin accessibility profiling and oxidative-stress manipulation

    PMID:28916653 PMID:29416634 PMID:41484137

    Open questions at the time
    • Link between GPX2 redox control and lineage transcription factors not fully mechanistic
    • Whether developmental and cancer roles share the same ROS thresholds unknown
  8. 2025 High

    Resolved the post-transcriptional and post-translational logic stabilizing GPX2, identifying PCBP2/METTL14/miR-185 control of mRNA and USP15/USP10 deubiquitination of protein at K187 as a hub driving drug resistance.

    Evidence RIP, m6A and miRNA analyses, Co-IP, ubiquitination assays with K187 mutant CRISPR-rescue, and xenograft/PDX models across colorectal and hepatocellular carcinoma

    PMID:23934683 PMID:35798180 PMID:37743483 PMID:40533443 PMID:42133228

    Open questions at the time
    • Coordination between mRNA and protein stabilization layers unclear
    • ACVRL1-USP15 recruitment kinetics and stoichiometry not defined
  9. 2025 Medium

    Connected GPX2-mediated redox balance to downstream oncogenic signaling and immune evasion, defining PI3K/AKT/mTOR/Snail, Hedgehog/GLI, NRF2-anti-ferroptosis, and MIF/CCL26-driven immunosuppressive axes.

    Evidence Gain/loss-of-function with pathway Western blots, GLI reporters, ferroptosis assays, single-cell/spatial transcriptomics, and in vivo tumor and anti-PD-1 combination models

    PMID:37287867 PMID:40089640 PMID:41106750 PMID:41939890

    Open questions at the time
    • Direct redox targets coupling ROS clearance to each signaling axis not biochemically defined
    • Mechanism of c-MYC nuclear-cytoplasmic redistribution and USP7-MIF stabilization lacks detailed validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GPX2's single biochemical activity — selective hydroperoxide reduction — is mechanistically partitioned to produce its diverse, context-specific outputs (homeostasis, inflammation, lineage choice, immune evasion) remains unresolved.
  • No structural basis for GPX2 substrate selectivity in cellular compartments
  • Direct redox-sensitive molecular targets linking H2O2 clearance to specific transcriptional/signaling responses not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 2 GO:0016491 oxidoreductase activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1266738 Developmental Biology 2
Partners
ACVRL1COX-2PCBP2USP10USP15

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 GPX2 (GSHPx-GI) is a selenium-dependent glutathione peroxidase that forms a tetrameric protein localized in the cytosol. It catalyzes the reduction of H2O2, tert-butyl hydroperoxide, cumene hydroperoxide, and linoleic acid hydroperoxide using glutathione as electron donor, but does not reduce phosphatidylcholine hydroperoxide. It does not cross-react with antisera against GPX1 or plasma GPX, establishing it as a distinct fourth member of the selenium-dependent GPX family. cDNA transfection/expression in MCF-7 cells, 75Se-labeling, SDS-PAGE, enzyme activity assays with multiple substrates, immunological cross-reactivity testing, subcellular fractionation The Journal of biological chemistry High 8428933
2001 GPX1 and GPX2 together provide the major glutathione peroxidase activity in intestinal epithelium; double knockout of both Gpx1 and Gpx2 in mice results in inflammatory bowel disease-like ileocolitis with elevated myeloperoxidase activity and lipid hydroperoxides in colon mucosa, whereas single knockout of either gene alone produces no overt phenotype under standard conditions. Targeted gene disruption (double knockout mice), histological examination, myeloperoxidase activity assay, lipid hydroperoxide measurement American journal of physiology. Gastrointestinal and liver physiology High 11518697
2004 Bacteria-induced intestinal inflammation is required for cancer development in GPX1/GPX2 double knockout mice; germ-free DKO mice have virtually no pathology or tumors, while colonization with commensal microflora (especially non-SPF conditions with Helicobacter) results in ileal and colonic adenocarcinomas, establishing that GPX2/GPX1 deficiency-driven carcinogenesis is bacteria-dependent. Germ-free mouse model, conventional/SPF/non-SPF colonization, histopathological analysis of tumor types Cancer research High 14871826
2006 GPX2 is a direct transcriptional target of p63 (but not p53); a unique p63-responsive element in the GPX2 promoter is activated and bound by p63 but not p53. GPX2 overexpression protects MCF7 cells from oxidative stress-induced apoptosis in a p53-dependent manner, and GPX2 deficiency renders MCF7 cells susceptible to oxidative stress-induced apoptosis. Promoter reporter assays, chromatin immunoprecipitation (ChIP), overexpression and siRNA knockdown, apoptosis assays in MCF7 cells The Journal of biological chemistry High 16446369
2007 The GPX2 promoter is activated by the β-catenin/TCF complex of the Wnt signaling pathway. The promoter contains five putative β-catenin/TCF binding sites; one site is sufficient for activation. Mutation of this site reduces response to β-catenin/TCF by more than 50%. Overexpression of wild-type APC in SW480 cells decreases basal GPX2 promoter activity. Promoter truncation and mutation reporter assays, β-catenin/TCF overexpression, APC overexpression in SW480 cells Biological chemistry High 17937616
2008 GPX2 knockdown in HT-29 colon cancer cells increases basal and IL-1-induced expression of COX-2 and mPGES-1, leading to elevated PGE2 release. GPX2 and COX-2 co-localize in the endoplasmic reticulum. This effect is specific to GPX2 (not reproduced by selenium deprivation which eliminates GPX1), indicating GPX2 suppresses pro-inflammatory PGE2 production by compartmentalized hydroperoxide removal. siRNA knockdown of GPX2 in HT-29 cells, Western blot for COX-2/mPGES-1, PGE2 ELISA, immunolocalization/co-localization studies Antioxidants & redox signaling High 18479189
2010 Loss of GPX2 in mice increases apoptosis at colonic crypt bases and expands the proliferative zone (increased mitotic cells in mid-crypt), establishing GPX2 as a regulator of mucosal homeostasis. GPX1 protein (but not mRNA) is upregulated in the colon and ileum of GPX2 KO mice, particularly at crypt bases, indicating compensatory post-translational upregulation of GPX1. GPX2 knockout mice, immunohistochemistry, apoptosis quantification, mitosis counting, immunohistochemistry for GPX1, qPCR for GPX1 mRNA Free radical biology & medicine High 20828612
2012 GPX2 expression in intestinal crypt bases is regulated by the Wnt signaling pathway in vivo and in vitro. In colonic crypt base cells, inducible knockout of β-catenin reduces basal GPX2 expression. GPX2 expression is consistently higher in proliferative crypt compartments where Wnt pathway is active. Wnt3a-overexpressing 3T3 cells, HT-29 APC cells (Wnt-inhibited), mouse crypt/villus fractionation, inducible β-catenin knockout in colonic crypt cells Biochimica et biophysica acta High 22683372
2014 GPX2 suppresses H2O2 stress in colorectal cancer colonosphere cultures; GPX2 silencing causes ROS accumulation, sensitization to H2O2-induced apoptosis, and strongly reduces clonogenic and metastasis-forming capacity. GPX2 overexpression stimulates multilineage differentiation, proliferation, and tumor growth. Neutralization of ROS restores clonogenic capacity in GPX2-silenced cells, placing GPX2's function upstream of ROS in maintaining tumor-initiating capacity. GPX2 silencing/overexpression in colonosphere cultures, ROS measurement, clonogenic assay, metastasis assay, ROS neutralization rescue experiment Cancer research High 25261240
2015 GPX2 promoter activity is induced by IL-22 through STAT transcription factors. Four putative STAT-responsive elements were identified in the GPX2 promoter; point mutation of the element nearest the transcription start site completely abolished promoter activation by IL-22 and by cotransfected STAT expression plasmids. GPX2 and phospho-STAT3 colocalize in inflamed colonic tissue during acute DSS colitis in vivo. GPX2 promoter reporter assays with STAT-element point mutations, STAT expression plasmid cotransfection, immunohistochemistry for phospho-STAT3/GPX2 co-localization in DSS colitis mouse model Inflammatory bowel diseases High 26115075
2016 Deficiency in Duox2 activity (via Duoxa knockout) in GPX1/GPX2 double knockout mice alleviates crypt exfoliation, crypt abscesses, goblet cell depletion, and growth retardation but does not prevent crypt apoptosis. This establishes that Duox2-generated ROS mediates crypt epithelium exfoliation (but not apoptosis) in GPX1/GPX2-deficient ileocolitis, placing GPX2/GPX1 and DUOX2 in the same pathway controlling intestinal epithelial integrity. Triple knockout mice (GPX1/2 DKO × Duoxa KO), histopathology, assessment of growth, crypt apoptosis, proliferation, goblet cells, Paneth cells Redox biology High 27930931
2017 YAP activation in lung squamous cell carcinoma leads to downregulation of GPX2 in a p63-dependent manner, resulting in excessive ROS accumulation. Digitoxin promotes YAP nuclear sequestration, attenuating YAP phosphorylation, which blocks the DNp63-GPX2 axis and increases ROS to suppress tumor growth. Small molecule screening, mechanistic studies of YAP/p63/GPX2 signaling, patient-derived xenograft models, ROS measurement Cancer research Medium 28916653
2017 Loss of GPX2 in mice alters intestinal cell fate decisions; proteomic analysis of GPX2 KO colonic tissue reveals downregulation of CLCA1 (goblet cell marker), CLCA2, CLCA3, stem cell marker Lgr5, enteroendocrine marker Chga, and intestinal hormones GLP1, ghrelin, and somatostatin, indicating GPX2 influences differentiation commitment in intestinal epithelium. Proteomic profiling of colonic tissue from GPX2 KO vs. WT mice, immunohistochemistry, mRNA expression analysis under varying selenium conditions Oncotarget Medium 29416634
2022 GPX2 is a downstream transcriptional target of β-catenin in hepatocellular carcinoma; lenvatinib prevents nuclear translocation of β-catenin, thereby inhibiting GPX2 expression. Loss of GPX2 increases intracellular ROS and apoptosis in HCC cells, while GPX2 overexpression reduces ROS and protects against lenvatinib-induced apoptosis. Microarray, qRT-PCR, gain/loss-of-function experiments, β-catenin nuclear translocation assay, ROS measurement, xenograft tumor model Journal of advanced research Medium 36725188
2023 ACVRL1 interacts directly with GPX2 protein (ACVRL1 truncation 282-503aa is responsible for this interaction). ACVRL1 associates with USP15, which deubiquitinates GPX2 at the K187 lysine residue, preventing GPX2 degradation and leading to GPX2 protein accumulation. Increased GPX2 stability enhances ROS clearance and reduces apoptosis, driving resistance to multitarget tyrosine kinase inhibitors in colorectal cancer. LC-MS protein interaction screen, Co-IP, ACVRL1 truncation mapping, ubiquitination assays, CRISPR KO of GPX2 with lysine mutant rescue experiments BMC medicine High 37743483
2025 USP10 directly binds to and deubiquitinates GPX2 protein, enhancing its stability. The USP10/GPX2 axis scavenges intracellular ROS to inhibit apoptosis and promote HCC cell survival under lenvatinib treatment, conferring drug resistance. Co-immunoprecipitation, ubiquitination assays, USP10 overexpression/knockdown, pharmacological inhibition (Spautin-1), ROS measurement, xenograft mouse model, RNA sequencing Cellular oncology (Dordrecht, Netherlands) High 42133228
2025 CBX3 suppresses CUL3 transcription by directly binding its promoter, preventing CUL3-mediated NRF2 ubiquitination and degradation. Stabilized NRF2 then drives GPX2 expression as a downstream effector. The CBX3/NRF2/GPX2 axis inhibits ferroptosis and promotes multidrug resistance in colorectal cancer. RNA sequencing, chromatin immunoprecipitation (ChIP), dual luciferase reporter assays, ubiquitination assays, GPX2 knockdown/overexpression, NRF2 inhibitor (ML385), PDX models Oncogene High 40089640
2025 N6-methyladenosine (m6A) modification on GPX2 mRNA mediated by METTL14 diminishes GPX2 mRNA stability. GPX2 promotes cancer stem cell characteristics and TKI resistance by triggering Hedgehog signaling activation through releasing GLI transcriptional regulator. GPX2 deletion constrains glutathione metabolism and enhances TKI efficacy in xenograft models. m6A modification analysis, METTL14 manipulation, Hedgehog pathway analysis, GLI reporter assays, xenograft models, gefitinib-resistant cell line models Cell death & disease Medium 40533443
2026 GPX2 is a critical regulator of human posterior foregut differentiation; GPX2 deficiency under pancreas-promoting conditions causes cells to also differentiate into hepatic-like progenitors. GPX2 deficiency triggers extracellular matrix remodeling, activating BMP signaling and skewing differentiation away from the pancreatic lineage. Manipulating oxidative stress levels recapitulates or rescues GPX2 loss effects, establishing oxidative stress as a gatekeeper of pancreatic cell fate. Bulk and single-cell transcriptomics, chromatin accessibility profiling (ATAC-seq), GPX2 loss-of-function in human pluripotent stem cell differentiation model, oxidative stress manipulation experiments Nature communications High 41484137
2025 GPX2 stabilizes MIF (macrophage migration inhibitory factor) expression through USP7-mediated deubiquitination in colorectal cancer cells, promoting macrophage M2 polarization and immune evasion. In vivo, GPX2 overexpression accelerates tumor growth associated with increased MIF signaling and M2 macrophage infiltration. Single-cell RNA sequencing, spatial transcriptomics, functional assays, mechanistic studies of USP7-MIF deubiquitination, in vivo tumor models International journal of biological macromolecules Medium 41106750
2022 PCBP2 (poly(rC) binding protein) binds to and stabilizes GPX2 mRNA. GPX2 exerts cytoprotective effects in esophageal cells through activation of autophagy; GPX2 silencing increases H2O2-induced apoptosis and LPS-induced inflammation, while GPX2 overexpression activates autophagy to protect cells. RIP (RNA-binding protein immunoprecipitation for PCBP2-GPX2 mRNA interaction), siRNA knockdown and overexpression of GPX2, apoptosis and inflammation assays, autophagy assessment Cellular signalling Medium 35798180
2013 miR-185 regulates GPX2 expression in intestinal cells; silencing of miR-185 increases GPX2 expression, establishing miR-185 as a negative post-transcriptional regulator of GPX2. miRNA microarray, RT-qPCR validation, miR-185 silencing in Caco-2 cells with measurement of GPX2 expression Molecular nutrition & food research Medium 23934683
2012 GPX2 and thioredoxin reductase 1 (TrxR1) cooperate to protect Caco-2 cells against H2O2-induced cell death; single and double knockdown of TrxR1 and/or GPX2 established that both selenoproteins are required for this cytoprotection via a ROS-dependent mechanism. siRNA single and double knockdown of TrxR1 and GPX2, cell viability assay after H2O2 treatment, ROS measurement Biochimica et biophysica acta Medium 22820176
2023 GPX2 promotes EMT and metastasis of NSCLC cells by reducing ROS accumulation and activating the PI3K/AKT/mTOR/Snail signaling axis. GPX2 knockdown inhibited metastasis in nude mice, while overexpression promoted migration and invasion in vitro. GPX2 overexpression and knockdown in NSCLC cell lines, ROS measurement, Western blot for PI3K/AKT/mTOR/Snail pathway components, in vitro migration/invasion assays, in vivo nude mouse metastasis model FASEB bioAdvances Medium 37287867
2025 GPX2 maintains cancer stem cell (CSC) characteristics intrinsically by mitigating ROS-mediated c-MYC nuclear-cytoplasmic redistribution. Extrinsically, GPX2 promotes immune evasion via the CCL26-CCR3 signaling axis, whereby GPX2-expressing tumor cells secrete CCL26 to recruit and polarize B cells toward an immunosuppressive LGALS1+ state. Single-cell RNA sequencing, functional assays (GPX2 overexpression, CCR3 targeting with ALK4290), in vivo tumor models, anti-PD-1 combination studies Frontiers in immunology Medium 41939890

Source papers

Stage 0 corpus · 66 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. The Journal of biological chemistry 393 8428933
2004 Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer research 241 14871826
2001 Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. American journal of physiology. Gastrointestinal and liver physiology 236 11518697
2006 GPX2, a direct target of p63, inhibits oxidative stress-induced apoptosis in a p53-dependent manner. The Journal of biological chemistry 142 16446369
2010 Loss of GPx2 increases apoptosis, mitosis, and GPx1 expression in the intestine of mice. Free radical biology & medicine 105 20828612
2017 YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation. Cancer research 78 28916653
2014 GPx2 suppression of H2O2 stress links the formation of differentiated tumor mass to metastatic capacity in colorectal cancer. Cancer research 78 25261240
2012 Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis. Annals of the New York Academy of Sciences 78 22758632
2005 GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae. The Journal of biological chemistry 74 16251189
1994 The human glutathione peroxidase genes GPX2, GPX3, and GPX4 map to chromosomes 14, 5, and 19, respectively. Cytogenetics and cell genetics 69 8287691
2008 GPx2 counteracts PGE2 production by dampening COX-2 and mPGES-1 expression in human colon cancer cells. Antioxidants & redox signaling 63 18479189
2007 Gpx2 is an overexpressed gene in rat breast cancers induced by three different chemical carcinogens. Cancer research 57 18056462
1995 The expression of an intestinal form of glutathione peroxidase (GSHPx-GI) in rat intestinal epithelium. Archives of biochemistry and biophysics 55 7487090
2013 Selenium alters miRNA profile in an intestinal cell line: evidence that miR-185 regulates expression of GPX2 and SEPSH2. Molecular nutrition & food research 52 23934683
2022 The beginning of GPX2 and 30 years later. Free radical biology & medicine 51 35803440
2012 The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium. Biochimica et biophysica acta 49 22683372
2022 GPX2 is a potential therapeutic target to induce cell apoptosis in lenvatinib against hepatocellular carcinoma. Journal of advanced research 47 36725188
2007 Activation of the glutathione peroxidase 2 (GPx2) promoter by beta-catenin. Biological chemistry 44 17937616
2004 Regulation of the yeast phospholipid hydroperoxide glutathione peroxidase GPX2 by oxidative stress is mediated by Yap1 and Skn7. FEBS letters 44 15135069
2007 A population-based association study of SNPs of GSTP1, MnSOD, GPX2 and Barrett's esophagus and esophageal adenocarcinoma. Carcinogenesis 43 17277236
2019 GPX2 silencing relieves epithelial-mesenchymal transition, invasion, and metastasis in pancreatic cancer by downregulating Wnt pathway. Journal of cellular physiology 41 31774184
1997 Expression and chromosomal mapping of mouse Gpx2 gene encoding the gastrointestinal form of glutathione peroxidase, GPX-GI. Biomedical and environmental sciences : BES 39 9315306
2022 Regulatory mechanism of α-hederin upon cisplatin sensibility in NSCLC at safe dose by destroying GSS/GSH/GPX2 axis-mediated glutathione oxidation-reduction system. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 35398749
2019 GPX2 suppression of H2O2 stress regulates cervical cancer metastasis and apoptosis via activation of the β-catenin-WNT pathway. OncoTargets and therapy 34 31695405
2016 Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium. Redox biology 34 27930931
2023 GPX2 promotes EMT and metastasis in non-small cell lung cancer by activating PI3K/AKT/mTOR/Snail signaling axis. FASEB bioAdvances 29 37287867
2010 Colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2. Inflammatory bowel diseases 29 20872835
1996 Polymorphism and chromosomal localization of the GI-form of human glutathione peroxidase (GPX2) on 14q24.1 by in situ hybridization. Genomics 29 8833155
2015 GPx2 Induction Is Mediated Through STAT Transcription Factors During Acute Colitis. Inflammatory bowel diseases 27 26115075
2022 GPX2 predicts recurrence-free survival and triggers the Wnt/β-catenin/EMT pathway in prostate cancer. PeerJ 26 36312753
2018 GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis. Oncotarget 24 29662611
2004 Distinct regulatory mechanism of yeast GPX2 encoding phospholipid hydroperoxide glutathione peroxidase by oxidative stress and a calcineurin/Crz1-mediated Ca2+ signaling pathway. FEBS letters 24 15225652
2000 Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional response to exogenous redox agents. Gene 23 10806356
2012 TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death. Biochimica et biophysica acta 21 22820176
2017 Loss of epithelium-specific GPx2 results in aberrant cell fate decisions during intestinal differentiation. Oncotarget 19 29416634
2023 ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization. BMC medicine 16 37743483
2021 Glutathione peroxidase 2 (Gpx2) preserves mitochondrial function and decreases ROS levels in chronologically aged yeast. Free radical research 14 33555225
2025 CBX3 promotes multidrug resistance by suppressing ferroptosis in colorectal carcinoma via the CUL3/NRF2/GPX2 axis. Oncogene 13 40089640
2023 Immunohistochemical Expression of Glutathione Peroxidase-2 (Gpx-2) and Its Clinical Relevance in Colon Adenocarcinoma Patients. International journal of molecular sciences 12 37834097
2019 The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial-like head and neck carcinoma subtypes. Head & neck 11 30652380
1996 The mouse glutathione peroxidase Gpx2 gene maps to chromosome 12; its pseudogene Gpx2-ps maps to chromosome 7. Genomics 10 8661011
2024 BRMS1L confers anticancer activity in non-small cell lung cancer by transcriptionally inducing a redox imbalance in the GPX2-ROS pathway. Translational oncology 9 38262108
2023 MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer. Cells 9 38132173
2013 The Gdac1 locus modifies spontaneous and Salmonella-induced colitis in mice deficient in either Gpx2 or Gpx1 gene. Free radical biology & medicine 9 24090658
2022 GPX2 stabilized by PCBP2 induces autophagy to protect Het-1A esophageal cells from apoptosis and inflammation. Cellular signalling 8 35798180
2022 GPX2 Gene Affects Feed Efficiency of Pigs by Inhibiting Fat Deposition and Promoting Muscle Development. Animals : an open access journal from MDPI 6 36552449
2025 X-ray-Sensitive Selenium Nanoparticles Enhance Esophageal Squamous Cell Carcinoma Radiotherapy through Activating P53/IGFBP3 Pathway by Regulating GPX2. ACS applied materials & interfaces 5 40241246
2024 NRF2 signaling plays an essential role in cancer progression through the NRF2-GPX2-NOTCH3 axis in head and neck squamous cell carcinoma. Oncogenesis 5 39333079
2023 GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/β-catenin pathway in colorectal cancer cells. Naunyn-Schmiedeberg's archives of pharmacology 5 37610461
2022 Native SodB Overexpression of Synechocystis sp. PCC 6803 Improves Cell Growth Under Alcohol Stresses Whereas Its Gpx2 Overexpression Impacts on Growth Recovery from Alcohol Stressors. Applied biochemistry and biotechnology 5 35819692
2025 GPX2 inhibition enhances antitumor efficacy of lenvatinib via promoting immunogenic cell death in hepatocellular carcinoma. Journal of translational medicine 4 40251668
2025 N6-methyladenosine-modified GPX2 impacts cancer cell stemness and TKI resistance through regulating of redox metabolism. Cell death & disease 4 40533443
2024 Overexpression of GPX2 gene regulates the development of porcine preadipocytes and skeletal muscle cells through MAPK signaling pathway. PloS one 3 38722949
2023 Long non-coding RNA NMRAL2P promotes glycolysis and reduces ROS in head and neck tumors by interacting with the ENO1 protein and promoting GPX2 transcription. PeerJ 3 37810778
2024 Evaluation of the Use of Cell Lines in Studies of Selenium-Dependent Glutathione Peroxidase 2 (GPX2) Involvement in Colorectal Cancer. Diseases (Basel, Switzerland) 2 39329876
2017 Individual expression features of GPX2, NQO1 and SQSTM1 transcript variants induced by hydrogen peroxide treatment in HeLa cells. Genetics and molecular biology 2 28558074
1998 Cloning and mapping of the mouse Gpx2 gene encoding gastrointestinal glutathione peroxidase. The Journal of veterinary medical science 2 9637305
2025 N6-Methyladenosine-Modified circNEK11 Promotes Hepatocellular Carcinoma Progression via the miR-1236-3p/GPX2 Axis. Cancer science 1 40990491
2025 GPX2 induces macrophage M2 polarization through the MIF signaling pathway to promote colorectal cancer progression. International journal of biological macromolecules 1 41106750
2025 HHLA3 transcriptionally promotes GPX2 to enhance anti-oxidative capacity by attenuating KEAP1-mediated NRF2 ubiquitination in lung adenocarcinoma. Free radical biology & medicine 1 41422997
2023 Effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on NRF2, KEAP1, SOD1, and GPX2 expression in human colorectal cancer cell lines. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 1 37075346
2026 Oxidative stress and GPX2 control pancreatic vs. non-pancreatic cell fate in human endoderm. Nature communications 0 41484137
2026 GPX2+ tumor cells recruit LGALS1+ B cells via CCL26-CCR3 axis to promote immunosuppression and tumor progression in hepatocellular carcinoma. Frontiers in immunology 0 41939890
2026 Dental pulp stem cell-derived exosomes attenuate psoriatic inflammation by restoring epithelial redox homeostasis via a miR-1246/miR-17-3p-GPX2-NF-κB axis. Stem cell research & therapy 0 42106764
2026 USP10 confers lenvatinib resistance in hepatocellular carcinoma by deubiquitinating the GPX2. Cellular oncology (Dordrecht, Netherlands) 0 42133228
2024 Mechanistic insights into 125I seed implantation therapy for Cholangiocarcinoma: focus on ROS-Mediated apoptosis and the role of GPX2. Journal of cancer research and clinical oncology 0 38914724

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