| 2004 |
NPGPx (GPX7) is a cytoplasmic protein (~22 kDa) that incorporates cysteine instead of selenocysteine at the conserved catalytic motif and has little detectable glutathione peroxidase activity in vitro. Re-expression of NPGPx in breast cancer cells conferred resistance to eicosapentaenoic acid-mediated oxidative cell death, while siRNA-mediated knockdown increased sensitivity, establishing a functional role in alleviating oxidative stress from polyunsaturated fatty acid metabolism. |
In vitro GPx activity assay, ectopic expression rescue, siRNA knockdown with cell viability readout |
The Journal of biological chemistry |
Medium |
15294905
|
| 2011 |
Under non-targeting siRNA (NT-siRNA) stress, NPGPx (GPX7) is selectively induced and covalently binds (via disulfide bond) to exoribonuclease XRN2, facilitating XRN2-mediated removal of accumulated NT-siRNA. NPGPx-depleted cells accumulated mature NT-siRNA and underwent apoptosis, demonstrating that NPGPx–XRN2 interaction is required to resolve NT-siRNA stress. |
Co-immunoprecipitation, covalent complex detection, siRNA knockdown with apoptosis and NT-siRNA accumulation readouts |
Nucleic acids research |
Medium |
21908404
|
| 2012 |
NPGPx (GPX7) acts as an oxidative stress sensor by forming an intramolecular disulfide bond between Cys57 and Cys86 in response to ROS. The oxidized form binds GRP78 and forms covalent intermediates between Cys86 of NPGPx and Cys41/Cys420 of GRP78, subsequently promoting the Cys41–Cys420 disulfide bond in GRP78 to enhance its chaperone activity. NPGPx-deficient cells show increased ROS, accumulated misfolded proteins, and impaired GRP78 chaperone activity. |
Mass spectrometry identification of disulfide bond sites, cysteine mutagenesis, Co-IP/covalent complex detection, in vitro chaperone activity assay, NPGPx-knockout cells/mice |
Molecular cell |
High |
23123197
|
| 2012 |
The proximal promoter of NPGPx (GPX7) contains a mixed G-quadruplex (G4) structure essential for NT-siRNA-induced transcriptional activation. Nucleolin (NCL) specifically binds the G4-containing sequences, replacing Sp1, to transactivate NPGPx expression under NT-siRNA stress; disrupting the G4 structure or depleting NCL abolished this induction. |
Promoter reporter assays with G4-disrupting mutations, ChIP, nucleolin overexpression/knockdown |
Nucleic acids research |
Medium |
23241391
|
| 2013 |
NPGPx (GPX7) deficiency promotes preadipocyte-to-adipocyte differentiation via ROS-dependent dimerization of protein kinase A (PKA) regulatory subunits and consequent activation of C/EBPβ. Antioxidant N-acetylcysteine treatment rescued the enhanced adipogenesis, placing GPX7 upstream of PKA regulatory subunit dimerization in the ROS–C/EBPβ axis. |
NPGPx-knockout mice and cells, PKA regulatory subunit dimerization assay, C/EBPβ activation assay, NAC rescue experiment, adipogenic differentiation assay |
EMBO molecular medicine |
High |
23828861
|
| 2015 |
NPGPx (GPX7) forms a disulfide bond with the translational regulator CPEB2, keeping CPEB2 associated with HIF-1α mRNA and suppressing its translation. Under high oxidative stress, this disulfide bond is disrupted, releasing CPEB2 from HIF-1α mRNA and allowing elevated HIF-1α translation. NPGPx-deficient cells show constitutively elevated HIF-1α translation under normoxia. |
Co-IP of disulfide-bonded NPGPx–CPEB2 complex, cysteine mutagenesis, polysome profiling/RNA-IP for HIF-1α mRNA association, NPGPx-KD cells |
Nucleic acids research |
Medium |
26446990
|
| 2017 |
GPX7 (and GPX8) are ER-resident peroxidases whose expression in rat β-cells attenuates FFA-mediated H2O2 generation, ER stress, and apoptosis. An ER-targeted catalase produced the same protective effect, establishing that accumulation of H2O2 in the ER lumen is the critical mediator of FFA-induced ER stress. GPX7/GPX8 expression did not increase disulfide bond formation in insulin, indicating H2O2 scavenging rather than oxidative protein folding is the primary protective function in β-cells. |
Stable expression of GPX7/GPX8 in INS-1E cells, ER-targeted catalase as comparator, H2O2 measurement, ER stress markers, apoptosis assays, insulin content/disulfide bond assays |
Free radical biology & medicine |
Medium |
28751022
|
| 2019 |
Stress-activated NPGPx (GPX7) inhibits O-GlcNAcase (OGA) through direct disulfide bond formation, thereby elevating global O-GlcNAcylation. In NPGPx-deficient motor neurons, OGA inhibition fails, O-GlcNAcylation cannot be boosted against age-dependent oxidative stress, and ROS accumulation leads to cell death. Pharmacological OGA inhibition rescued motor neuron loss in aged NPGPx-deficient mice, placing NPGPx upstream of OGA in this neuroprotective axis. |
NPGPx-KO mice (ALS-like phenotype), disulfide bond Co-IP between NPGPx and OGA, pharmacological OGA inhibitor rescue in vivo, O-GlcNAcylation western blot |
Cell reports |
High |
31747588
|
| 2020 |
Human GPX7 has much higher reactivity with H2O2 than GPX8, owing to a catalytic tetrad at its redox-active site that stabilizes the sulfenylated peroxidatic cysteine intermediate. A resolving cysteine (not the peroxidatic cysteine) regulates GPX7's PDI oxidation activity. In H2O2-treated cells, GPX7 preferentially forms complexes with PDI and P5, functioning as an H2O2-dependent PDI oxidase for oxidative protein folding. |
In vitro H2O2 reactivity assays, PDI oxidation activity assays, active-site mutagenesis, Co-IP of GPX7 with PDI/P5 in H2O2-treated cells |
The Journal of biological chemistry |
High |
32719007
|
| 2020 |
GPX7 knockdown in TGF-β/FFA-treated hepatic stellate cells (LX-2) elevated pro-fibrotic and pro-inflammatory gene expression and collagen synthesis, while GPX7 overexpression suppressed ROS and reduced these responses. In vivo, GPX7 knockdown accelerated NASH fibrosis in CDAHFD-fed mice, establishing GPX7 as a negative regulator of hepatic stellate cell activation and fibrosis via ROS suppression. |
siRNA knockdown and overexpression in LX-2 cells, ROS measurement, fibrosis/inflammation gene expression, in vivo CDAHFD mouse model with hepatic GPX7 knockdown |
BMB reports |
Medium |
32317079
|
| 2021 |
NPGPx (GPX7) deficiency in BMSCs reduces osteogenic differentiation and increases adipogenic differentiation. Unlike adipogenesis (which is ROS-dependent), inhibition of osteogenesis by GPX7 deficiency is mediated through elevated ER stress (rescued by ER stress antagonist, not ROS inhibitor), and involves downregulation of mTOR signaling that can be rescued by relief of ER stress. |
GPX7-deficient human BMSCs and mouse MSC line, osteogenic/adipogenic differentiation assays, ER stress antagonist and ROS inhibitor rescue experiments, mTOR pathway western blot |
Journal of cellular and molecular medicine |
Medium |
34626080
|
| 2021 |
NPGPx (GPX7) restrains ZAP70 kinase activity in T cells through direct disulfide bond formation with ZAP70 (identified by proteomic approaches). ROS generated upon TCR stimulation activate NPGPx, which reduces ZAP70 recruitment to the TCR/CD3 complex in membrane lipid rafts, thereby subduing TCR responses. T cell-specific NPGPx-knockout mice show hyperproliferation, elevated cytokines, enhanced humoral responses, and susceptibility to EAE. |
Proteomic identification of NPGPx–ZAP70 disulfide complex, T cell-specific KO mice, TCR signaling assays, lipid raft fractionation, EAE model |
Free radical biology & medicine |
High |
33460768
|
| 2016 |
GPX7 (NPGPx) functions as a redox stress sensor/transmitter that lacks GPx activity but shuttles disulfide bonds to interacting proteins (GRP78, PDI, CPEB2, XRN2) in response to oxidative and other cellular stresses, thereby modulating unfolded protein response, oxidative stress signaling, and non-targeting siRNA stress response. |
Review/synthesis of prior experimental findings from the same group (no new primary experiments described) |
American journal of translational research |
Low |
27186289
|