| 2003 |
Prdx1 knockout mice develop severe haemolytic anaemia characterized by increased erythrocyte ROS, protein oxidation, haemoglobin instability, Heinz body formation, and decreased erythrocyte lifespan, establishing PRDX1 as an essential antioxidant defence in erythrocytes. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, and Prdx1-null mice have abnormalities in NK cell numbers, phenotype, and function. |
Targeted gene knockout in mice with phenotypic characterization (ROS measurement, haematological assays, tumour histopathology, NK cell functional assays) |
Nature |
High |
12891360
|
| 2009 |
PRDX1 physically interacts with the transmembrane protein GDE2 and activates it by reducing an intramolecular disulfide bond bridging GDE2's intracellular N- and C-terminal domains, thereby driving spinal motor neuron differentiation. This activation requires PRDX1's thiol-dependent catalytic activity, and GDE2 variants incapable of disulfide bond formation become independent of PRDX1. |
Co-immunoprecipitation, in vivo loss-of-function (Prdx1 knockdown/knockout in chick spinal cord), active-site mutagenesis of PRDX1 and GDE2, epistasis analysis |
Cell |
High |
19766572
|
| 2013 |
PRDX1 binds to both MKP-1 and MKP-5 phosphatases in an H2O2 dose-dependent manner via its peroxidatic cysteine Cys52. At high H2O2, over-oxidation of Cys52 to sulfonic acid causes PRDX1 to dissociate from MKP-1, leading to MKP-1 oxidation-induced oligomerization and inactivation toward p38MAPKα, while the PRDX1:MKP-5 complex is stabilized, protecting MKP-5 from inactivation. This mechanism coordinates p38MAPK-dependent cellular senescence in breast epithelial cells. |
Co-immunoprecipitation, H2O2 dose-response assays, Cys52 mutagenesis, p38MAPK phosphorylation assays, ROS-induced senescence model |
Oncogene |
High |
23334324
|
| 2018 |
PRDX1 interacts with the RING finger domain of TRAF6 and inhibits its ubiquitin-ligase activity, thereby suppressing ubiquitination of ECSIT (required for NF-κB activation) and BECN1 (required for autophagy). PRDX1 knockdown increases NF-κB activation, pro-inflammatory cytokine production, and bactericidal autophagy. |
Co-immunoprecipitation, ubiquitination assays in PRDX1-knockdown cell lines (THP-1, MDA-MB-231, SK-HEP-1), TLR4 stimulation experiments |
Autophagy |
High |
29929436
|
| 2018 |
PRDX1 and MTH1 cooperate to prevent accumulation of oxidized guanine in the genome. Concomitant disruption of PRDX1 and MTH1 in cancer cells causes ROS-dependent continuous telomere shortening due to efficient inhibition of telomere extension by telomerase, identifying PRDX1 as a guardian of telomere integrity. |
CRISPR gene disruption, telomere length measurement, ROS quantification, telomerase extension assays |
Genes & development |
High |
29773556
|
| 2018 |
Kinetic analysis established that the peroxidatic cysteine of PRDX1 reacts ~10-fold faster with H2O2 than peroxynitrite (both orders of magnitude faster than typical protein thiols), and that PRDX1 has a substantially faster disulfide formation rate (11 s⁻¹) than PRDX2 (0.2 s⁻¹), which determines its distinct redox-relay function versus PRDX2's mixed-disulfide signaling mode. The additional C83 residue in PRDX1 further differentiates its response to peroxynitrite. |
In vitro kinetic assays using recombinant human PRDX1 and PRDX2, intrinsic fluorescence monitoring of oxidation and hyperoxidation |
Protein science |
High |
30284335
|
| 2013 |
Pin1 binds PRDX1 through the phospho-Thr90-Pro91 motif and facilitates PP2A-mediated dephosphorylation of PRDX1, restoring its peroxidase activity. In Pin1-knockout MEFs, phosphorylated (Thr90) PRDX1 accumulates in its inactive form, leading to increased H2O2 buildup. |
Proteomic pulldown, co-immunoprecipitation, Thr90 mutagenesis, peroxidase activity assay in Pin1−/− MEFs with Pin1 re-introduction, H2O2 measurement |
Cell cycle |
High |
23421996
|
| 2020 |
PRDX1 is enriched in telomeric chromatin and counteracts ROS-induced telomere damage. In PRDX1-depleted cells, PARP-dependent telomeric repair is often incomplete, generating persistent single-strand breaks that are converted to double-strand breaks during replication. PARP1 inhibition in PRDX1-depleted cells dampens telomere shortening by stabilising BRCA1 and enabling RAD51-mediated HR repair. |
PRDX1 depletion, telomere ChIP showing PRDX1 enrichment, PARP inhibitor epistasis, telomere length assays, SSB/DSB quantification |
Cell reports |
High |
33147465
|
| 2021 |
PRDX1 binds TRAF6 and BECN1 and deficiency in PRDX1 suppresses autophagic flux in macrophages, leading to impaired lipophagic cholesterol hydrolysis, higher intracellular cholesterol, and reduced cholesterol efflux. 2-Cys PRDX mimics (ebselen, gliotoxin) rescue these defects, and Prdx1-deficient bone marrow transplantation into apoe-/- mice increases atherosclerotic plaque formation. |
Prdx1 knockout macrophages, lipophagic flux assays, cholesterol efflux assays, in vivo bone marrow transplant model, pharmacological rescue |
Autophagy |
High |
28605287
|
| 2013 |
AMPK activation stabilises the interaction between c-Abl and PRDX1, preventing oxidative stress-induced dissociation of the complex. Knockdown of PRDX1 increases phosphorylation of both caveolin-1 and c-Abl and abolishes the inhibitory effect of AMPK on caveolin-1 phosphorylation and albumin endocytosis in endothelial cells. |
Co-immunoprecipitation, siRNA knockdown, pharmacological AMPK activation (AICAR), caveolin-1 phosphorylation and endocytosis assays |
The Journal of biological chemistry |
Medium |
23723070
|
| 2021 |
PRDX1 oligomers bind both the Nedd8-conjugating enzyme UBE2F and CUL5, forming a tricomplex essential for CUL5 neddylation. This promotes NOXA ubiquitination and degradation, inhibiting apoptosis in colorectal cancer cells. ROS elevation drives PRDX1 oligomerization, linking oxidative stress to NOXA protein half-life. |
Co-immunoprecipitation, PRDX1 oligomerization assays, ubiquitination assays, NOXA protein half-life measurement, PRDX1 knockdown and oligomerization inhibition |
Cell death & disease |
Medium |
33712558
|
| 2018 |
PRDX1 forms a heterodimer with p38α (MAPK14), stabilizing phospho-p38α in glioma cells, which amplifies HGF-mediated MET signaling and stimulates actin cytoskeleton dynamics to promote glioma cell migration and brain invasion in vivo. |
Biochemical interaction studies (Co-IP), in vitro and ex vivo migration assays, whole-brain high-resolution ultramicroscopy in mouse glioma models, survival analysis of PRDX1-KD mice |
International journal of cancer |
Medium |
29582423
|
| 2021 |
PRDX1 interacts with ASK1 at elevated H2O2 concentrations in a manner that does not require a scaffolding protein, in contrast to the Prdx2:STAT3 relay. This interaction was demonstrated both in cellulo and by in vitro protein-protein interaction methods. |
Co-immunoprecipitation, in vitro pulldown, H2O2 dose-response experiments |
Antioxidants (Basel, Switzerland) |
Medium |
34209102
|
| 2024 |
The lysine acetyltransferase MOF acetylates PRDX1 at lysine 197 (K197), preventing its hyperoxidation and maintaining peroxidase activity under inflammatory stress. LPS stimulation rapidly decreases PRDX1 K197ac in macrophages, elevating H2O2, augmenting ERK1/2 phosphorylation, stimulating glycolysis, and enhancing pro-inflammatory IL-6 production. |
Identification of K197 acetylation site, MOF KO/knockdown experiments, LPS stimulation, H2O2 measurement, ERK1/2 phosphorylation assays, metabolic flux analysis |
Cell reports |
High |
39207899
|
| 2024 |
HJURP forms disulfide-linked intermediates with PRDX1 through Cys327 and Cys457 residues of HJURP, promoting PRDX1 redox cycling and inhibiting its hyperoxidation, thereby enhancing PRDX1 peroxidase activity and suppressing ROS and lipid peroxidation to confer ferroptosis resistance in prostate cancer cells. |
Co-immunoprecipitation, disulfide bond identification by mutagenesis, peroxidase activity assays, ROS and lipid peroxidation measurement, in vivo xenograft |
Redox biology |
Medium |
39405980
|
| 2023 |
During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage-induced nuclear ROS. Loss of PRDX1 lowers aspartate availability, impairing DNA damage-induced upregulation of de novo nucleotide synthesis, and causes accumulation of replication stress and DNA damage. |
Functional genomics (CRISPR screen), chromatin proteomics, metabolomics, nuclear fractionation/localization, etoposide treatment experiments |
Molecular systems biology |
High |
37259925
|
| 2024 |
PRDX1 acts as a molecular chaperone by binding to CUL3, inhibiting CUL3-mediated NRF2 ubiquitination and stabilising NRF2, which drives GPX4 transcription. The Cys83 residue of PRDX1 is required for CUL3 binding and this activity is enhanced by conoidin A. |
IP-MS, Co-immunoprecipitation, Cys83Ser mutagenesis, ubiquitination assays, NRF2 nuclear translocation assays, PRDX1 KO mouse model (AOM/DSS) |
International journal of biological sciences |
High |
39430237
|
| 2019 |
PRDX1 binds JNK1 and inhibits JNK kinase signaling, thereby suppressing the cancer-associated fibroblast (CAF)-like activated phenotype in mammary fibroblasts. Loss of PRDX1 results in development of a CAF-like phenotype that is reversed by JNK inhibition. |
Co-immunoprecipitation of PRDX1 with JNK1, PRDX1 knockout mouse fibroblasts, JNK inhibitor (SP600125) rescue, migration/invasion assays |
BMC cancer |
Medium |
31419957
|
| 2023 |
The lncRNA LncFASA directly binds the Ahpc-TSA domain of PRDX1 and drives liquid-liquid phase separation of PRDX1 into droplets, inhibiting its peroxidase activity. This disrupts ROS homeostasis and promotes ferroptosis through the SLC7A11-GPX4 axis in triple-negative breast cancer cells. |
RNA-protein binding assays, phase separation assays, peroxidase activity assays, SLC7A11/GPX4 pathway analysis, xenograft tumor model |
Science China. Life sciences |
Medium |
37955780
|
| 2020 |
Prdx1 regulates the HEF1-Aurora A-HDAC6 signaling axis to promote primary cilia disassembly in esophageal squamous cell carcinoma cells; silencing Prdx1 restores primary cilia formation and reduces tumor formation in vivo. |
Prdx1 siRNA knockdown, gene chip analysis, cilia formation assays, HEF1/Aurora A/HDAC6 pathway measurement, in vivo xenograft |
BMC cancer |
Medium |
32357862
|
| 2020 |
Prdx1 functions as an RNA-binding protein that stabilises inflammation- and apoptosis-related mRNAs after intracerebral haemorrhage, as identified by RIP-seq. Prdx1 overexpression reduces inflammation and apoptosis in ICH models. |
RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq), AAV-mediated overexpression in rat ICH model |
Frontiers in neuroscience |
Medium |
32210752
|
| 2024 |
Hspb1 directly interacts with Anxa2 to reduce its aggregation and phosphorylation, which in turn allows Anxa2 to interact with Prdx1 and maintain its antioxidative activity by decreasing Thr-90 phosphorylation of Prdx1; overexpression of Hspb1 had no protective effect in acinar-specific Prdx1 knockout mice, establishing the Hspb1/Anxa2/Prdx1 axis. |
Co-immunoprecipitation, Prdx1 acinar cell-specific KO mice, AAV8-Hspb1 overexpression, Thr-90 phosphorylation assays, genetic epistasis |
International journal of biological sciences |
Medium |
38481805
|
| 2023 |
PRDX1 Cys52Ser (peroxidase-dead) variant mice show impaired global PRDX peroxidase activity and are protected from diet-induced NASH and liver fibrosis, with suppressed NF-κB and STAT1 pro-inflammatory signalling, demonstrating that peroxidatic Cys52 is required for PRDX1's pro-inflammatory activity in vivo. |
Knock-in mouse model (Cys52Ser), Trx-TrxR-NADPH coupled activity assay, western diet/MCD diet feeding, RNA-seq, NF-κB and STAT1 pathway analysis |
Molecular metabolism |
High |
37562742
|
| 2023 |
Kinetic modelling established that the PRDX1 dimer-to-decamer transition (association rate 0.050 µM⁻⁴·s⁻¹, dissociation rate 0.055 s⁻¹) has an inhibition-like effect on peroxidase activity, as the decameric form has ~100-fold lower activity than the dimer. Incorporating this transition into an in vivo PRDX model reconciled experimental and simulated oxidation-state responses. |
Isothermal titration calorimetry data fitting, kinetic modelling, HRP competition and NADPH-oxidation assays, in vivo PRDX2 erythrocyte model simulation |
Antioxidants (Basel, Switzerland) |
Medium |
37760010
|
| 2024 |
ZNF207 promotes lactylation of PRDX1 at lysine 67, which enhances PRDX1 nuclear translocation and activation of NRF2, creating a ferroptosis-resistant environment in HCC cells and driving regorafenib resistance. |
CRISPR/Cas9 screening, lactylation site identification (K67), nuclear translocation assays, NRF2 activity assays, RGF sensitivity rescue experiments |
Drug resistance updates |
Medium |
40680452
|
| 2021 |
IRAK1 binds PRDX1 and prevents its ubiquitination and degradation mediated by the E3 ubiquitin ligase HECTD3 (which interacts with PRDX1 via its DOC and HECT domains). Overexpression of PRDX1 reverses the radiosensitisation effect of IRAK1 depletion by diminishing autophagic cell death in glioma. |
Co-IP, LC-MS/MS, GST pulldown, ubiquitination assays, domain-mapping mutagenesis of HECTD3, PRDX1 overexpression rescue |
Cell death & disease |
Medium |
37031183
|
| 2024 |
PRDX1 directly interacts with the actin-binding protein Cofilin, inhibiting phosphorylation of Cofilin at Ser3, thereby accelerating actin depolymerisation and turnover and promoting OSCC cell migration and invasion. |
Co-immunoprecipitation, Cofilin Ser3 phosphorylation assays, actin dynamics assays, in vitro migration/invasion, nude mouse tongue cancer model |
International journal of cancer |
Medium |
38738971
|
| 2025 |
A co-crystal structure of PRDX1 with the celastrol derivative LC-PDin20 revealed the binding mode of covalent inhibitors with PRDX1, and active cysteine residues were confirmed as the covalent binding sites, enabling structure-based design of selective PRDX1 inhibitors. |
Co-crystal structure determination (X-ray crystallography), molecular docking, in vitro PRDX1 enzyme inhibition assay (IC50 determination) |
Journal of medicinal chemistry |
High |
40546088
|
| 2024 |
Recombinant PRDX1 protein dose-dependently inhibits ROS production and osteoclast differentiation from bone marrow macrophages, and mechanistically attenuates NFATc1 activation as well as expression of C-Fos, V-ATPase-d2, Cathepsin K, and Integrin αV downstream of RANKL signalling. |
Recombinant protein treatment, ROS measurement, osteoclast differentiation assay, NFATc1 and downstream marker expression analysis |
Journal of cellular physiology |
Medium |
39263840
|
| 2023 |
BACH1 directly binds the promoter region of PRDX1 and inhibits its transcription; remifentanil treatment suppresses BACH1 and upregulates PRDX1, thereby reducing oxidative stress injury in hepatic ischaemia-reperfusion. |
Chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, BACH1 overexpression and PRDX1 silencing epistasis |
Clinics and research in hepatology and gastroenterology |
Medium |
39025461
|
| 2025 |
NFAT5 directly binds the PRDX1 promoter to drive its transcription, which enhances mitochondrial function in cervical cancer cells. METTL3 promotes NFAT5 mRNA stability via IGF2BP3-mediated m6A modification, placing PRDX1 downstream of an m6A-NFAT5 transcriptional regulatory axis. |
ChIP assay, dual-luciferase reporter assay, MeRIP assay, NFAT5 knockdown/overexpression with PRDX1 rescue |
Journal of biochemical and molecular toxicology |
Medium |
39925026
|