| 2003 |
Prdx1 knockout mice develop severe haemolytic anaemia with increased erythrocyte ROS, protein oxidation, haemoglobin instability, and Heinz body formation, demonstrating Prdx1's essential role as an 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 and function. |
Targeted gene inactivation (knockout mouse), phenotypic analysis including erythrocyte ROS measurement, haemoglobin stability assay, Heinz body staining, NK cell functional assays |
Nature |
High |
12891360
|
| 2009 |
Prdx1 interacts with the transmembrane protein GDE2 and activates it through reduction of an intramolecular disulfide bond bridging GDE2's intracellular N- and C-terminal domains; this thiol-redox-dependent activation is required for spinal motor neuron differentiation. GDE2 variants incapable of disulfide bond formation are constitutively active and independent of Prdx1, establishing catalytic mechanism. |
Co-immunoprecipitation, genetic loss-of-function (Prdx1 and GDE2 ablation), active-site mutagenesis of Prdx1 (thiol-dead variants), GDE2 disulfide bond-null mutants, motor neuron differentiation assays in chick spinal cord |
Cell |
High |
19766572
|
| 2013 |
Prdx1 binds to both MKP-1 and MKP-5 (MAPK phosphatases). When its peroxidatic cysteine Cys52 is over-oxidised to sulfonic acid, Prdx1 dissociates from MKP-1, leading to MKP-1 oxidation-induced oligomerisation and inactivation toward p38MAPKα. Conversely, over-oxidised Prdx1 enhances the Prdx1:MKP-5 complex, protecting MKP-5 from inactivation, thereby maintaining MKP-5 activity toward p38MAPK and controlling ROS-induced senescence in breast epithelial cells. |
Co-immunoprecipitation, active-site mutant analysis (Cys52), H2O2 dose-response experiments, p38MAPKα activity assays in human breast epithelial cells |
Oncogene |
Medium |
23334324
|
| 2013 |
Pin1 binds to the phospho-Thr90-Pro91 motif of PRDX1 and facilitates PP2A-mediated dephosphorylation of PRDX1, thereby restoring its peroxidase activity. In Pin1-/- MEFs, PRDX1 accumulates in an inactive phosphorylated form, leading to increased H2O2 and decreased peroxidase activity, which is rescued by re-introduction of Pin1. |
Proteomic identification of Pin1 binding partners, co-immunoprecipitation, Thr90 mutagenesis, Pin1 knockout MEFs, Pin1 rescue experiments, peroxidase activity assay |
Cell cycle (Georgetown, Tex.) |
Medium |
23421996
|
| 2013 |
PRDX1 associated with c-Abl kinase under basal conditions; oxidative stress promotes dissociation of the Prdx1:c-Abl complex, leading to c-Abl activation and subsequent caveolin-1 phosphorylation and albumin endocytosis. AMPK activation suppresses this pathway by stabilising the Prdx1:c-Abl interaction. Prdx1 knockdown increased phosphorylation of both c-Abl and caveolin-1 and abolished AMPK's inhibitory effect. |
Co-immunoprecipitation, siRNA knockdown of Prdx1 and c-Abl, pharmacological AMPK activation/inhibition, caveolin-1 phosphorylation assay, albumin endocytosis assay in HUVEC cells |
The Journal of biological chemistry |
Medium |
23723070
|
| 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 in THP-1, MDA-MB-231, and SK-HEP-1 cells increased NF-κB activation, pro-inflammatory cytokines, and enhanced cancer cell migration/invasion. |
Co-immunoprecipitation (PRDX1 with TRAF6 RING domain), ubiquitination assay for ECSIT and BECN1, PRDX1 knockdown (siRNA), NF-κB reporter assay, cytokine ELISA, migration/invasion assay |
Autophagy |
Medium |
29929436
|
| 2018 |
PRDX1 and MTH1 cooperate to prevent accumulation of oxidised guanine in the genome. Concomitant disruption of PRDX1 and MTH1 genes in cancer cells leads to ROS-dependent continuous telomere shortening due to inhibition of telomerase-mediated telomere extension by oxidised guanine. |
CRISPR gene disruption of PRDX1 and MTH1, telomere length measurement, telomerase activity assay, ROS quantification |
Genes & development |
High |
29773556
|
| 2018 |
PRDX1 forms a heterodimer with p38α (MAPK14), stabilising phospho-p38α in glioma cells. This complex amplifies HGF/MET-driven signalling and promotes actin cytoskeleton dynamics and glioma cell migration in vitro and invasion in vivo. |
Biochemical interaction studies (co-immunoprecipitation), in vitro and ex vivo migration assays, whole-brain ultramicroscopy, mouse glioma survival models |
International journal of cancer |
Medium |
29582423
|
| 2018 |
Differential kinetics between PRDX1 and PRDX2: the rate of disulfide formation (resolution step) is 11 s⁻¹ for PRDX1 vs 0.2 s⁻¹ for PRDX2, making PRDX1 less susceptible to hyperoxidation and directing it toward a classical disulfide relay rather than a sulfenic-acid-mediated redox relay used by PRDX2. |
In vitro kinetic assays with recombinant human PRDX1 and PRDX2, intrinsic fluorescence monitoring of oxidation and hyperoxidation by H2O2 and peroxynitrite |
Protein science : a publication of the Protein Society |
High |
30284335
|
| 2020 |
PRDX1 is enriched in telomeric chromatin. In PRDX1-depleted cells, PARP-dependent telomeric repair is often incomplete, generating persistent single-strand breaks that are converted into double-strand breaks during replication, causing rapid telomere shortening. PARP1 inhibition dampens this telomere shortening by promoting BRCA1/RAD51-mediated homologous recombination repair. |
PRDX1 depletion (siRNA/CRISPR), telomeric chromatin ChIP, PARP inhibition, telomere length assays, DNA damage marker assays |
Cell reports |
Medium |
33147465
|
| 2021 |
PRDX1 oligomers bind with both the Nedd8-conjugating enzyme UBE2F and CUL5, forming a tricomplex critical for CUL5 neddylation. This promotes ubiquitination and degradation of the pro-apoptotic protein NOXA. Silencing PRDX1 or inhibiting PRDX1 oligomerisation greatly dampened CUL5 neddylation and extended the NOXA protein half-life. |
Co-immunoprecipitation, PRDX1 knockdown, PRDX1 oligomerisation inhibition, NOXA ubiquitination and protein stability assays, CUL5 neddylation assay |
Cell death & disease |
Medium |
33712558
|
| 2021 |
Prdx1 interacts with ASK1 at elevated H2O2 concentrations independently of a scaffolding protein, constituting a redox-relay. This differs from the Prdx2:STAT3 relay and the Prdx2:ASK1 interaction (which requires a facilitator that is not annexin A2). |
Co-immunoprecipitation in cells, in vitro protein-protein interaction assays, H2O2 dose-response, comparison with Prdx2 |
Antioxidants (Basel, Switzerland) |
Medium |
34209102
|
| 2022 |
18β-glycyrrhetinic acid covalently binds to active cysteine residues of PRDX1 (and PRDX2), inhibiting their peroxidase activities, leading to ROS elevation and apoptosis in activated hepatic stellate cells. PRDX1 knockdown alone also produced ROS-mediated apoptosis. |
Activity-based protein profiling (chemoproteomic), cellular thermal shift assay, surface plasmon resonance, PRDX1 knockdown, enzymatic activity assay |
Journal of pharmaceutical analysis |
Medium |
36105163
|
| 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 replication stress accumulation. |
Functional genomics screen integrated with chromatin proteomics and metabolomics, PRDX1 KO, nuclear fractionation/localisation experiments, aspartate and nucleotide metabolite measurements |
Molecular systems biology |
Medium |
37259925
|
| 2023 |
LncFASA directly binds to the Ahpc-TSA domain of PRDX1 and drives liquid-liquid phase separation of PRDX1, forming droplets that inhibit its peroxidase activity and disrupt ROS homeostasis, thereby promoting ferroptosis via the SLC7A11-GPX4 axis. |
RNA-protein binding assay (Ahpc-TSA domain mapping), phase separation droplet assay, PRDX1 peroxidase activity assay, SLC7A11-GPX4 pathway analysis, xenograft tumor model |
Science China. Life sciences |
Medium |
37955780
|
| 2024 |
MOF acetyltransferase acetylates PRDX1 at lysine 197 (K197), preventing its hyperoxidation and maintaining peroxidase activity under stress. LPS-induced inflammatory signalling rapidly decreases PRDX1 K197 acetylation in macrophages, elevating H2O2 accumulation, augmenting ERK1/2 phosphorylation, stimulating glycolysis, and enhancing pro-inflammatory mediator production (IL-6). |
Identification of MOF as PRDX1 acetyltransferase, K197 acetylation mass spectrometry, MOF KO macrophages, LPS stimulation, hyperoxidation assays, ERK1/2 phosphorylation, metabolic (glycolysis) assays |
Cell reports |
High |
39207899
|
| 2024 |
HJURP forms disulfide-linked intermediates with PRDX1 through its Cys327 and Cys457 residues, promoting PRDX1 redox cycling and inhibiting its hyperoxidation, thereby enhancing PRDX1 peroxidase activity and reducing ROS/lipid peroxidation to suppress ferroptosis in prostate cancer cells. |
Co-immunoprecipitation, disulfide bond formation assay, mutagenesis of HJURP cysteines, PRDX1 peroxidase activity assay, ROS and lipid peroxidation measurements, in vitro and in vivo ferroptosis assays |
Redox biology |
Medium |
39405980
|
| 2024 |
PRDX1 acts as a molecular chaperone by binding to CUL3, inhibiting CUL3-mediated NRF2 ubiquitination, thereby promoting NRF2 nuclear translocation and transcription of GPX4. This chaperone binding requires PRDX1 Cys83; the Cys83Ser mutant abolishes CUL3 binding. Conoidin A enhances CUL3 binding. |
IP-mass spectrometry, Co-immunoprecipitation (PRDX1 with CUL3), Cys83Ser mutagenesis, NRF2 ubiquitination assay, PRDX1 KO mice (AOM/DSS CRC model), RNA sequencing, GPX4 transcription assay |
International journal of biological sciences |
High |
39430237
|
| 2024 |
Hspb1 directly interacts with Anxa2 to decrease its aggregation and phosphorylation, enabling Anxa2 to interact with Prdx1 and maintain its antioxidative activity by decreasing Prdx1 Thr90 phosphorylation. Overexpression of Hspb1 did not protect against pancreatitis in acinar-specific Prdx1 knockout mice, establishing Prdx1 as the downstream effector. |
Co-immunoprecipitation (Hspb1 with Anxa2 and Prdx1), Anxa2 KO mice, acinar-specific Prdx1 KO mice, Thr90 phosphorylation assay, AAV8-Hspb1 rescue experiments |
International journal of biological sciences |
Medium |
38481805
|
| 2024 |
PRDX1 directly interacts with the actin-binding protein Cofilin, inhibiting phosphorylation of Cofilin at Ser3, thereby accelerating actin depolymerisation and turnover, promoting oral squamous cell carcinoma cell movement, invasion, and metastasis. |
Co-immunoprecipitation (PRDX1 with Cofilin), Cofilin Ser3 phosphorylation assay, actin dynamics assay, in vitro migration/invasion assays, nude mouse tongue cancer model |
International journal of cancer |
Medium |
38738971
|
| 2024 |
IRAK1 binds to PRDX1 and prevents ubiquitination and proteasomal degradation of PRDX1 mediated by the E3 ubiquitin ligase HECTD3. Both the DOC and HECT domains of HECTD3 directly interact with PRDX1. |
IP/Co-IP, LC-MS/MS, GST pull-down, ubiquitination assay, HECTD3 domain mapping |
Cell death & disease |
Medium |
37031183
|
| 2025 |
ZNF207 promotes lactylation of PRDX1 at lysine 67, which enhances PRDX1 nuclear translocation and activation of NRF2, creating a ferroptosis-resistant environment and conferring regorafenib resistance in HCC cells. Disrupting PRDX1 K67 lactylation or NRF2 activity reverses resistance. |
CRISPR/Cas9 screening, lactylation modification assay (K67 site), nuclear fractionation/localisation, NRF2 activity assay, ferroptosis functional assays, drug resistance assays |
Drug resistance updates |
Medium |
40680452
|
| 2025 |
Artesunate directly binds to PRDX1 (interacting at Gly4) and PRDX2, inhibiting their peroxidase activities and inducing ferroptosis in diffuse large B-cell lymphoma cells. PRDX1 knockdown reproduced ferroptosis and reduced sensitivity to artesunate; PRDX2 overexpression attenuated artesunate-induced ROS and cytotoxicity. |
Small-molecule pull-down/LC-MS/MS, CETSA, fluorescence titration, circular dichroism, molecular docking, PRDX1/2 knockdown and overexpression, peroxidase activity assay, xenograft model |
Cell death & disease |
High |
40645965
|
| 2025 |
A co-crystal structure of PRDX1 with the celastrol derivative LC-PDin20, combined with molecular docking, revealed the binding mode of covalent inhibitors to PRDX1 active site, enabling structure-based design of selective PRDX1 inhibitors. |
Co-crystal structure determination, molecular docking, in vitro PRDX1 enzymatic inhibition assay (IC50 determination), cell antiproliferation assay |
Journal of medicinal chemistry |
High |
40546088
|
| 2017 |
Prdx1 deficiency impairs lipophagic flux in macrophages by causing excessive oxidative stress, leading to reduced free cholesterol formation, decreased NR1H3 (LXRα) activity, and lower cholesterol efflux. 2-Cys PRDX mimics ebselen and gliotoxin restored both lipophagic flux and cholesterol efflux in Prdx1-deficient macrophages. |
Prdx1 KO macrophages, autophagic flux assay, cholesterol efflux assay, NR1H3 activity assay, ebselen/gliotoxin rescue, bone marrow transplant into apoe-/- mice with plaque measurement |
Autophagy |
Medium |
28605287
|
| 2019 |
PRDX1 inhibits the activated (cancer-associated) fibroblast phenotype by binding to JNK1 and regulating JNK kinase signalling; loss of PRDX1 results in development of a CAF-like phenotype in mammary fibroblasts. JNK inhibition with SP600125 reduced CAF-like behaviors in Prdx1 KO fibroblasts. |
Co-immunoprecipitation (PRDX1 with JNK1), PRDX1 KO mouse fibroblasts, JNK inhibitor (SP600125), transwell migration/invasion assay, immunofluorescence |
BMC cancer |
Medium |
31419957
|
| 2021 |
PRDX1 activates autophagy in spiral ganglion neurons at least partially through activation of the PTEN-AKT signalling pathway; PRDX1 deficiency suppresses autophagy and increases neuronal loss after cisplatin exposure, while PRDX1 upregulation (pharmacologically or by AAV) activates autophagy and reduces ROS accumulation. |
PRDX1 KO and AAV-mediated overexpression, autophagy flux assay (LC3B, p62), PTEN/AKT pathway western blot, ROS measurement, SGN survival and hearing function assays |
Autophagy |
Medium |
33749526
|
| 2023 |
PRDX1 Cys52Ser (peroxidase-dead) variant mice show impaired global PRDX peroxidase activity and reduced susceptibility to diet-induced NASH and liver fibrosis. Mechanistically, the Cys52Ser variant suppresses NF-κB and STAT1 signalling, indicating that PRDX1 peroxidatic Cys52 is required for its pro-inflammatory activity in vivo. |
Knock-in mouse (PRDX1 Cys52Ser), Trx-TrxR-NADPH coupled peroxidase activity assay, western diet/MCD diet NASH model, RNA sequencing, NF-κB and STAT1 pathway analysis |
Molecular metabolism |
High |
37562742
|
| 2024 |
PRDX1 interacts with DOK3 and modulates DOK3 degradation via the autophagy-lysosome pathway, thereby inhibiting plasma cell differentiation. The small molecule Salvianolic acid B acts as a molecular glue enhancing the PRDX1-DOK3 interaction, further impairing plasma cell differentiation and collagen-induced arthritis progression. |
Co-immunoprecipitation (PRDX1-DOK3), autophagy-lysosome pathway inhibition assay, plasma cell differentiation assay, collagen-induced arthritis mouse model, small molecule (SAB) functional validation |
Acta pharmaceutica Sinica. B |
Medium |
40893682
|
| 2023 |
Modelling shows that the PRDX1 dimer-to-decamer transition has an inhibition-like effect on peroxidase activity; association and dissociation rate constants of 0.050 µM⁻⁴·s⁻¹ and 0.055 s⁻¹ respectively were obtained from isothermal titration calorimetry data and incorporated into kinetic models. |
Kinetic modelling using isothermal titration calorimetry data, HRP competition assay simulation, NADPH-oxidation linked assay simulation |
Antioxidants (Basel, Switzerland) |
Low |
37760010
|
| 2025 |
BACH1 directly binds to the PRDX1 promoter region and inhibits PRDX1 transcription. Remifentanil treatment inactivates BACH1, relieving PRDX1 repression and thereby reducing oxidative stress in hepatic ischemia-reperfusion injury. |
Chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, PRDX1 silencing rescue, HIRI mouse model, mRNA microarray |
Clinics and research in hepatology and gastroenterology |
Medium |
39025461
|