Affinage

PARK7

Parkinson disease protein 7 · UniProt Q99497

Length
189 aa
Mass
19.9 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PARK7/DJ-1 is a redox-responsive, homodimeric protein that functions as a cytoprotective hub coordinating antioxidant defense, mitochondrial quality control, and cell-death suppression, with its activity gated by oxidation of a conserved Cys106 residue (PMID:21852238, PMID:25833141). As an oxidative-stress effector it drives the Nrf2 pathway, stabilizing Nrf2 and enhancing its recruitment to antioxidant response elements to induce thioredoxin 1 and proteasome subunits, with pathogenic mutants L166P and M26I unable to support this induction (PMID:22492997, PMID:25833141). DJ-1 binds and inhibits the 20S proteasome to spare partially unfolded substrates such as α-synuclein and p53 from degradation (PMID:25833141). It sustains mitochondrial function by binding complex I subunits NDUFA4 and ND1 (PMID:19822128) and acts downstream of PINK1/parkin during selective mitophagy, translocating to depolarized mitochondria to enable optineurin recruitment (PMID:36039535) and licensing Parkin S-nitrosylation (PMID:32152416). DJ-1 stabilizes HIF-1α by interacting with VHL and inhibiting its E3 ligase activity (PMID:24899725), preserves the SAHH tetramer to support transsulfuration-dependent glutathione synthesis and suppress ferroptosis (PMID:32144268), and binds PDHB to promote pyruvate dehydrogenase activity and oxidative phosphorylation in regulatory T cells (PMID:35618940). In an oxidation-dependent manner it binds and stabilizes BCL-XL to suppress apoptosis (PMID:21852238). Beyond intracellular roles, DJ-1 negatively regulates RANKL-driven osteoclastogenesis through SHP-1 activation (PMID:29142196), restrains NADPH oxidase ROS production by binding p47phox (PMID:27735193), and, when released from necrotic cells, acts as an extracellular DAMP activating TLR2/TLR4 (PMID:34014921); it is secreted via an autophagy-based unconventional pathway under oxidative stress (PMID:30112966). A reported nucleotide/protein deglycase activity (PMID:28596309) is reframed by rigorous kinetics as glyoxalase-like with only a minor role in neuronal methylglyoxal defense (PMID:35713360).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 Medium

    Established a direct biochemical link between DJ-1 and mitochondrial bioenergetics by showing it physically associates with complex I subunits and is required for full complex I activity.

    Evidence Co-IP, colocalization, and complex I activity assays in DJ-1-knockdown NIH3T3 and HEK293 cells

    PMID:19822128

    Open questions at the time
    • Does not define whether binding directly stabilizes the complex or acts through assembly/repair
    • Single lab; no structural model of the DJ-1–complex I interface
  2. 2009 Medium

    Positioned DJ-1 upstream of HIF1 by demonstrating that its loss reduces HIF1-responsive transcription via diminished Akt/mTOR and altered AMPK signaling.

    Evidence siRNA and knockout MEFs with HIF1 reporters and phospho-signaling blots

    PMID:19144925

    Open questions at the time
    • Mechanism of mTOR/AMPK regulation not molecularly resolved
    • Relationship to the later VHL-based HIF stabilization mechanism unclear
  3. 2011 Medium

    Defined an oxidation-gated anti-apoptotic mechanism in which Cys106-oxidized DJ-1 binds and stabilizes BCL-XL against ubiquitin-proteasome degradation.

    Evidence Co-IP, fractionation, ubiquitination assay, Cys106 mutagenesis, and caspase readouts under UVB stress

    PMID:21852238

    Open questions at the time
    • E3 ligase targeting BCL-XL not identified
    • Single lab; in vitro reconstitution of oxidation-dependent binding lacking
  4. 2012 High

    Showed DJ-1 transduces antioxidant gene expression by driving Nrf2 stabilization, nuclear translocation, and ARE occupancy to induce thioredoxin 1, with pathogenic mutants unable to do so.

    Evidence Promoter reporter, ChIP, siRNA rescue, and DJ-1 knockout mice

    PMID:22492997

    Open questions at the time
    • Direct molecular step by which DJ-1 raises Nrf2 levels not defined
    • Generalizability beyond Trx1 to the full ARE program not delineated
  5. 2015 High

    Identified DJ-1 as a proteasome regulator that binds and inhibits the 20S proteasome to rescue partially unfolded substrates, linking it to proteostasis.

    Evidence Co-IP, in vitro proteasome activity assay, substrate stabilization blots, and Nrf2 reporter assays

    PMID:25833141

    Open questions at the time
    • Structural basis of 20S binding/inhibition unresolved
    • Selectivity of which substrates are rescued not fully defined
  6. 2014 High

    Provided a molecular mechanism for HIF-1α stabilization by showing DJ-1 binds VHL and inhibits its E3 ligase activity, with HIF-1α rescue protecting DJ-1-deficient neurons.

    Evidence Co-IP, in vitro ubiquitination, HIF-1α stability and rescue assays, patient lymphoblast validation

    PMID:24899725

    Open questions at the time
    • How DJ-1 inhibits VHL catalytically not defined
    • Reconciliation with the mTOR/AMPK-based HIF mechanism not addressed
  7. 2013 Medium

    Extended DJ-1's anti-oxidative role to proline metabolism by showing it binds and enhances PYCR1 activity on a shared protective pathway.

    Evidence In vivo and in vitro Co-IP, colocalization, enzyme activity, and double-knockdown epistasis

    PMID:23743200

    Open questions at the time
    • Structural basis of activation not defined
    • In vivo relevance not tested
  8. 2017 Medium

    Proposed an enzymatic deglycase function repairing methylglyoxal/glyoxal glycation on nucleotides and DNA, with depletion increasing glycated DNA and DNA damage.

    Evidence In vitro deglycase assays, mass spectrometry, and γH2AX/p53 readouts in depleted cells

    PMID:28596309

    Open questions at the time
    • Catalytic mechanism contested by later kinetic analysis
    • Cellular DNA-repair role not separated from indirect effects
  9. 2022 Medium

    Reframed the deglycase claim through rigorous kinetics, supporting a glyoxalase-like activity with only a minor role in neuronal methylglyoxal defense.

    Evidence In vitro kinetics, computational modeling, isotope-dilution MS in neurons/brain, and viability assays

    PMID:35713360

    Open questions at the time
    • Physiological substrate and in vivo glycation burden not fully resolved
    • Single lab counter-finding
  10. 2016 High

    Defined DJ-1 as an essential downstream node of PINK1/parkin mitophagy required for optineurin recruitment, with translocation independent of Cys106 oxidation.

    Evidence Loss-of-function in human fibroblasts and iPSC neurons with homozygous PARK7 mutations, mitophagy flux, and live imaging

    PMID:36039535

    Open questions at the time
    • Molecular mechanism of optineurin recruitment by DJ-1 not defined
    • Direct binding partners on depolarized mitochondria not identified
  11. 2020 Medium

    Showed DJ-1 is indispensable for Parkin S-nitrosylation, linking it to a redox PTM controlling mitochondrial stress survival.

    Evidence 2D-DIGE, S-nitrosylation detection, genome-edited DJ-1-null and Parkin Cys-mutant cells, mitochondrial assays

    PMID:32152416

    Open questions at the time
    • Whether DJ-1 acts enzymatically or as a scaffold for nitrosylation unknown
    • NO source/transnitrosylase chain not defined
  12. 2020 High

    Connected DJ-1 to ferroptosis suppression by showing it preserves the SAHH tetramer to sustain transsulfuration and glutathione synthesis.

    Evidence Metabolomics, metabolite rescue, Co-IP, native gels of SAHH, ferroptosis assays in vitro and in vivo

    PMID:32144268

    Open questions at the time
    • Structural basis for tetramer stabilization unresolved
    • Whether redox state of DJ-1 gates this function not tested
  13. 2022 High

    Demonstrated a metabolic role in immunity by showing DJ-1 binds PDHB to inhibit PDHA phosphorylation, promoting PDH-driven OXPHOS and Treg fitness.

    Evidence Co-IP, PDH activity, OXPHOS profiling, conditional KO mice, and EAE model

    PMID:35618940

    Open questions at the time
    • How binding blocks PDHA phosphorylation mechanistically unclear
    • Relationship to DJ-1 redox state not addressed
  14. 2017 High

    Identified DJ-1 as a negative regulator of osteoclastogenesis acting through SHP-1 to suppress RANK signaling, establishing a skeletal role.

    Evidence DJ-1 KO mice bone phenotype, BMM osteoclast assays, SHP-1 activity assays, and disease models

    PMID:29142196

    Open questions at the time
    • How DJ-1 activates SHP-1 molecularly not defined
    • Direct binding between DJ-1 and SHP-1 not shown
  15. 2017 High

    Showed DJ-1 restrains macrophage ROS by binding p47phox to disrupt NADPH oxidase assembly and promote Nox2 degradation, balancing antioxidant and antimicrobial functions.

    Evidence Co-IP, Nox2 ubiquitination assay, DJ-1 KO BMMs/mice, and adoptive transfer

    PMID:27735193

    Open questions at the time
    • E3 ligase mediating Nox2 degradation not identified
    • Structural interface with p47phox unresolved
  16. 2021 High

    Defined an extracellular function in which necrosis-released DJ-1 acts as a DAMP activating TLR2/TLR4 to drive post-ischemic inflammation.

    Evidence Recombinant DJ-1 cytokine assays, peptide mapping of αG/αH helices, DJ-1 KO MCAO model, neutralizing antibody

    PMID:34014921

    Open questions at the time
    • Structural basis of TLR engagement not crystallographically resolved
    • Whether oxidation state alters DAMP activity not addressed
  17. 2018 Medium

    Established how DJ-1 reaches the extracellular space, showing oxidative stress triggers AMPK-ULK1–driven autophagy-based unconventional secretion of DJ-1.

    Evidence Secreted DJ-1 ELISA, ATG5/9/16L1 KO/KD, AMPK/ULK1 blots, and NAC rescue

    PMID:30112966

    Open questions at the time
    • Carrier/membrane intermediate of secretion not defined
    • Link to the DAMP function not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single redox-sensing fold integrates its many context-specific partner interactions, and whether Cys106 oxidation universally gates them or only a subset of functions.
  • No unified structural framework linking the diverse binding partners
  • Tissue-specific determinants of which pathway DJ-1 engages are unknown
  • Causal contribution of each pathway to PARK7-linked parkinsonism not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0016209 antioxidant activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140098 catalytic activity, acting on RNA 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005576 extracellular region 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
BCL2L1HTTNCF1NDUFA4PDHBPYCR1RACK1VHL

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 DJ-1 directly binds to NDUFA4 and ND1, nuclear- and mitochondrial DNA-encoded subunits of mitochondrial complex I, respectively, colocalizes with complex I, and knockdown of DJ-1 in NIH3T3 and HEK293 cells reduces complex I activity. Co-immunoprecipitation, colocalization studies, enzymatic activity assay in DJ-1-knockdown cells Biochemical and biophysical research communications Medium 19822128
2016 DJ-1 is an essential downstream mediator of PINK1/parkin-mediated mitophagy; loss of DJ-1 blocks mitophagy by inhibiting recruitment of the selective autophagy receptor optineurin to depolarized mitochondria, without interfering with PINK1 or parkin activation. DJ-1 translocates to depolarized mitochondria in a PINK1/parkin-dependent manner, and this translocation does not require oxidation of Cys106. Loss-of-function experiments in human fibroblasts and iPSC-derived neurons with homozygous PARK7 mutations; mitophagy flux assays; live-cell imaging of DJ-1 translocation Brain : a journal of neurology High 36039535
2011 Oxidized DJ-1 (dependent on Cys106 oxidation) increases its mitochondrial distribution in response to UVB irradiation and binds BCL-XL; this interaction stabilizes BCL-XL protein by inhibiting its ubiquitination and proteasomal degradation, thereby suppressing apoptosis. DJ-1 C106A mutant binds BCL-XL much less. Co-immunoprecipitation, subcellular fractionation, ubiquitination assay, siRNA knockdown, caspase activation assays The Journal of biological chemistry Medium 21852238
2015 DJ-1 physically binds the 20S proteasome and inhibits its proteolytic activity, rescuing partially unfolded proteins (including α-synuclein and p53) from degradation. Under oxidative stress, DJ-1 also participates in Nrf2-dependent upregulation of both the 20S proteasome and its regulator NQO1. Co-immunoprecipitation, in vitro proteasome activity assay, western blotting of proteasome substrates, Nrf2 pathway reporter assays Nature communications High 25833141
2012 Wild-type DJ-1 induces expression of thioredoxin 1 (Trx1) via the Nrf2 pathway; DJ-1 overexpression increases Nrf2 protein levels, promotes Nrf2 nuclear translocation, and enhances Nrf2 recruitment to the antioxidant response element (ARE) in the Trx1 promoter. Pathogenic mutants L166P and M26I cannot induce Trx1. Nrf2 knockdown abolishes DJ-1-mediated Trx1 induction and cytoprotection. Promoter reporter assay, chromatin immunoprecipitation, siRNA knockdown, western blotting, DJ-1 knockout mice Human molecular genetics High 22492997
2017 DJ-1 and its bacterial homologs (Hsp31, YhbO, YajL) repair methylglyoxal- and glyoxal-glycated nucleotides and nucleic acids in vitro; DJ-1-depleted cells displayed increased levels of glycated DNA, DNA strand breaks, and phosphorylated p53, indicating a nucleotide/DNA glycation repair (deglycase) function. In vitro biochemical deglycase assay, mass spectrometry quantification of glycated DNA, γH2AX and p53 phosphorylation readout in DJ-1-depleted cells Science (New York, N.Y.) Medium 28596309
2022 DJ-1 reduces levels of reversible adducts of methylglyoxal (MG) with guanine and cysteine in vitro, consistent with glyoxalase activity; however, computational kinetic modeling supports glyoxalase (not true deglycase) as the mechanism. DJ-1 modestly reduces irreversible guanine and lysine glycation products in neurons but does not improve cell viability against exogenous MG, indicating DJ-1 is not a bona fide deglycase and has only a minor role in neuronal methylglyoxal defense. In vitro kinetic assays, computational kinetic modeling, isotope-dilution mass spectrometry in primary neurons and mouse brain, cell viability assay Journal of neurochemistry Medium 35713360
2009 DJ-1 loss reduces transcription of HIF1-responsive genes during hypoxia and decreases Akt and mTOR activities that sustain HIF1α stability; DJ-1 also regulates AMPK activity especially during hypoxia. DJ-1 is thus positioned as an upstream activator of HIF1 function via mTOR and AMPK. DJ-1 loss-of-function (siRNA and knockout MEFs), HIF1 transcriptional reporter assays, western blotting for Akt/mTOR/AMPK phosphorylation, cell death assays Proceedings of the National Academy of Sciences of the United States of America Medium 19144925
2014 DJ-1 interacts with VHL protein and negatively regulates VHL's ubiquitin E3 ligase activity toward HIF-1α, thereby inhibiting HIF-1α degradation. DJ-1 deficiency leads to lowered HIF-1α levels under hypoxia and oxidative stress, and HIF-1α accumulation rescues DJ-1-deficient neurons from MPP+-induced toxicity. Co-immunoprecipitation, in vitro ubiquitination assay, HIF-1α stability assays in DJ-1-deficient neurons, neuronal rescue experiments, patient lymphoblast validation The Journal of neuroscience : the official journal of the Society for Neuroscience High 24899725
2020 DJ-1 suppresses ferroptosis by preserving the activity of S-adenosyl homocysteine hydrolase (SAHH) tetramer; DJ-1 depletion disrupts SAHH tetramer formation and impairs its enzymatic activity, inhibiting the transsulfuration pathway and reducing homocysteine (and thus glutathione) biosynthesis when cystine uptake is blocked. Metabolic analysis, metabolite rescue assays, co-immunoprecipitation, native gel electrophoresis of SAHH tetramer, ferroptosis cell death assays in vitro and in vivo Nature communications High 32144268
2022 DJ-1 binds to PDHB (PDHE1-β), the regulatory subunit of pyruvate dehydrogenase (PDH), inhibiting phosphorylation of PDHA (PDHE1-α), thereby promoting PDH activity and oxidative phosphorylation in CD4+ regulatory T cells (Tregs). Park7 deletion impairs Treg survival and reduces Treg homeostatic proliferation in aged mice. Co-immunoprecipitation of DJ-1 with PDHB, PDH activity assay in DJ-1-knockout T cells, OXPHOS metabolic profiling, conditional KO mouse models, EAE disease model Nature metabolism High 35618940
2017 DJ-1 deficiency leads to an age-dependent accumulation of hexokinase 1 in the cytosol (away from mitochondria) and subsequent activation of the polyol pathway in rodent brain; DJ-1 deficiency is also associated with accumulation of PTEN (antagonizing AKT), and inhibiting hexokinase-mitochondria association or AKT suppresses the PINK1/parkin mitophagy pathway. Unbiased proteomic, transcriptomic, and metabolomic screens in DJ-1 KO rat and mouse brain; targeted hexokinase localization assays; cellular epistasis with kinase inhibitors and hexokinase-dissociating peptides Molecular neurodegeneration Medium 28962651
2020 DJ-1 is indispensable for the S-nitrosylation of Parkin; DJ-1 deletion inhibits S-nitrosylation of endogenous and overexpressed Parkin in neuroblastoma cells and mouse brain, and cells with DJ-1 deletion or S-nitrosylation-deficient Parkin mutation share phenotypes of increased cell death under mitochondrial depolarization and mitochondrial dysfunction. 2D-DIGE proteomics, S-nitrosylation detection assay, genome-edited DJ-1-null and Parkin Cys-mutant neuroblastoma cells, mitochondrial function assays Scientific reports Medium 32152416
2018 DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability at CNS nerve terminals without causing structural synaptic alterations; familial DJ-1 mutants (M26I, E64D, L166P) cannot rescue endocytic defects, whereas WT DJ-1 fully restores endocytosis in DJ-1 KO neurons. The mechanism involves altered membrane cholesterol levels. Synaptic vesicle endocytosis assays (FM dye recycling) in DJ-1 KO neurons, rescue with WT and mutant DJ-1 constructs, cholesterol quantification Proceedings of the National Academy of Sciences of the United States of America Medium 29386384
2017 DJ-1 deficiency in mice reduces CMA-associated degradation of α-synuclein by accelerating degradation of LAMP2A in lysosomes and downregulating lysosomal HSC70 levels, thereby impairing CMA and increasing α-synuclein accumulation and aggregation. DJ-1 knockout mice, DJ-1 siRNA in SH-SY5Y cells, LAMP2A and HSC70 western blotting in lysosomal fractions, α-synuclein aggregation assays Frontiers in aging neuroscience Medium 29021755
2017 DJ-1 negatively regulates RANKL-driven osteoclast differentiation (osteoclastogenesis) by activating the phosphatase SHP-1, which in turn suppresses both RANK-TRAF6 and RANK-FcRγ/Syk signaling pathways. DJ-1 ablation in mice decreases bone volume and increases osteoclast numbers. DJ-1 KO mice (bone phenotype), in vitro BMM osteoclastogenesis assays, SHP-1 activity assays, phospho-signaling western blots, arthritis and RANKL-induced bone disease models Nature communications High 29142196
2013 DJ-1 directly binds to PYCR1 (pyrroline-5-carboxylate reductase 1) in vivo and in vitro; both proteins colocalize in mitochondria, and DJ-1 enhances PYCR1 enzymatic activity. Knockdown of either DJ-1 or PYCR1 reduces cell viability under oxidative stress; combined knockdown of both produces no additive effect, placing them on the same anti-oxidative stress pathway. Co-immunoprecipitation (in vivo and in vitro pulldown), colocalization by immunofluorescence, PYCR1 enzyme activity assay, genetic epistasis (double knockdown) Biochemical and biophysical research communications Medium 23743200
2013 DJ-1 directly interacts with expanded huntingtin exon 1 (httEx1) in cell-free and cell-based experiments and accelerates polyglutamine aggregation and toxicity in an oxidation-sensitive manner; DJ-1 overexpression is protective against neurodegeneration in yeast and Drosophila HD models. In vitro pulldown, cell-based co-immunoprecipitation, yeast and Drosophila overexpression models, aggregation assays Human molecular genetics Medium 24070869
2017 DJ-1 binds p47phox, a critical component of the NADPH oxidase complex, disrupting NADPH oxidase complex assembly and facilitating Nox2 (gp91phox) ubiquitination and degradation, thereby inhibiting ROS production and impairing optimal bactericidal activity in macrophages. Co-immunoprecipitation (DJ-1/p47phox interaction), Nox2 ubiquitination assay, DJ-1 KO BMMs and mice (ROS/bacterial killing phenotype), adoptive transfer experiments American journal of respiratory and critical care medicine High 27735193
2013 DJ-1 epigenetically regulates eNOS expression in vascular endothelial cells; DJ-1 knockout increases HDAC-1 recruitment and decreases H3 histone acetylation at the eNOS promoter, reducing NO production and eNOS expression, leading to impaired vasorelaxation and elevated systolic blood pressure. Chromatin immunoprecipitation (HDAC-1 and acetyl-H3 at eNOS promoter), NO quantification, eNOS western blot, DJ-1 KO mice with blood pressure measurement, pharmacological HDAC inhibitor rescue Cardiovascular research Medium 24323315
2014 DJ-1 interacts with RACK1 (receptor of activated C kinase 1), increases RACK1 dimerization and protein stability, and the DJ-1-RACK1 complex protects cortical neurons from H2O2-induced apoptosis; H2O2 or MPP+ treatment disrupts the DJ-1/RACK1 interaction. Co-immunoprecipitation, overexpression and knockdown rescue experiments in cortical neurons, apoptosis assays The Biochemical journal Low 24947010
2021 DJ-1 is released from necrotic neurons into the extracellular space after ischemia and functions as a damage-associated molecular pattern (DAMP) activating Toll-like receptor 2 (TLR2) and TLR4 on infiltrating myeloid cells via a specific peptide sequence in the αG and αH helices of DJ-1, thereby inducing post-ischemic cerebral inflammation. Recombinant DJ-1 cytokine induction assay in BMMs/BMDCs, TLR2/TLR4 binding identification (peptide mapping), DJ-1 KO MCAO mouse model, neutralizing antibody experiment PLoS biology High 34014921
2018 DJ-1 secretion is induced by 6-OHDA via an autophagy-based unconventional secretory pathway; 6-OHDA-derived electrophilic quinone induces oxidative stress (GSH depletion) and activates AMPK-ULK1 signaling (independent of mTOR), leading to secretory autophagy and unconventional secretion of DJ-1. Knockdown or knockout of ATG5, ATG9, or ATG16L1 suppresses 6-OHDA-induced DJ-1 secretion. Secreted DJ-1 ELISA, autophagy-deficient MEF cells and siRNA knockdown, AMPK/ULK1 phosphorylation western blot, NAC antioxidant rescue Autophagy Medium 30112966
2012 DJ-1 promotes differentiation of human mesenchymal stem cells to osteoblasts and induces angiogenesis in endothelial cells through activation of fibroblast growth factor receptor-1 (FGFR1) signaling; these effects are blocked by antagonizing FGFR1 signaling. Osteoblast and angiogenesis differentiation assays, FGFR1 inhibitor rescue, rodent bone fracture repair model with extracellular DJ-1 application Nature communications Medium 23250426
2016 Glutaredoxin 1 (Grx1) regulates DJ-1 protein levels in vivo; two sites of glutathionylation were identified on isolated DJ-1 protein, and DJ-1 protein content decreases in response to glutathionylating agents in neuronal cells. Overexpression of DJ-1 in dopaminergic neurons partly compensates for loss of the Grx1 homologue in C. elegans. Grx1 KO mice (DJ-1 protein level measurement), in vitro glutathionylation site mapping by mass spectrometry, C. elegans in vivo genetic rescue Biochemistry Medium 26894491
2017 DJ-1 exerts anti-inflammatory effects in ischemic astrocytes by facilitating the interaction between SHP-1 and TRAF6, thereby inducing the dissociation of NLRX1 from TRAF6 and suppressing downstream inflammatory signaling (TNF-α, IL-1β, IL-6). Co-immunoprecipitation (SHP-1/TRAF6 and NLRX1/TRAF6 interactions), SHP-1 inhibitor experiments, DJ-1 knockdown in OGD/R astrocytes, MCAO/R in vivo model Journal of neuroinflammation Medium 32151250
2012 DJ-1 deficiency in mast cells (DJ-1 KO mice) suppresses SHP-1 activity and enhances SHP-2 activity, leading to strengthened signaling through LAT, PLCγ, and MAPKs, and augmenting antigen-induced degranulation and cytokine (TNF-α, IL-4) production; DJ-1 KO mice exhibit enhanced passive cutaneous anaphylaxis. DJ-1 KO mice, bone marrow-derived mast cell cultures, siRNA knockdown of SHP-1/SHP-2, immunoblotting, passive cutaneous anaphylaxis in vivo The Journal of allergy and clinical immunology Medium 23182168
2004 Crystal structure of the E64D DJ-1 mutant shows the mutation does not alter the overall protein structure, but the mutant shows a tendency toward decreased protein levels when overexpressed in HEK293 or COS7 cells. The L166P mutant (but not E64D) causes predominant nuclear localization in ~80% of expressing cells. X-ray crystallography, overexpression in HEK293/COS7 cells, immunocytochemistry for subcellular localization Human mutation Medium 15365989
2014 DJ-1 promotes breast cancer cell invasion by downregulating KLF17 expression and its target ID-1, thereby reducing E-cadherin and increasing Snail expression; KLF17 overexpression overcomes DJ-1-induced invasion, and DJ-1 cooperates with Ras to increase cell invasion. DJ-1 siRNA and overexpression in breast cancer cells, ID-1 promoter luciferase assay, epistasis analysis (KLF17 overexpression rescue), Ras inhibitor experiments, invasion assays British journal of cancer Medium 24504364

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. Brain : a journal of neurology 384 14662519
2003 DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 306 14598065
2013 Neuroprotective function of DJ-1 in Parkinson's disease. Oxidative medicine and cellular longevity 300 23766857
2011 The role of cysteine oxidation in DJ-1 function and dysfunction. Antioxidants & redox signaling 266 20812780
2020 DJ-1 suppresses ferroptosis through preserving the activity of S-adenosyl homocysteine hydrolase. Nature communications 217 32144268
2007 Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. Current opinion in neurobiology 209 17499497
2019 Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease. Journal of bioenergetics and biomembranes 207 31054074
2009 DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proceedings of the National Academy of Sciences of the United States of America 187 19144925
2009 DJ-1 binds to mitochondrial complex I and maintains its activity. Biochemical and biophysical research communications 171 19822128
2012 DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway. Human molecular genetics 169 22492997
2006 PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. Neurobiology of disease 160 16860563
2004 DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease. Neurology 150 14872018
2017 Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science (New York, N.Y.) 146 28596309
2012 Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 135 22956510
2019 DJ-1 in Parkinson's Disease: Clinical Insights and Therapeutic Perspectives. Journal of clinical medicine 134 31484320
2022 DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain : a journal of neurology 125 36039535
2017 DJ-1 Inhibits α-Synuclein Aggregation by Regulating Chaperone-Mediated Autophagy. Frontiers in aging neuroscience 108 29021755
2015 The Parkinson's-associated protein DJ-1 regulates the 20S proteasome. Nature communications 107 25833141
2014 DJ-1 as a human oncogene and potential therapeutic target. Biochemical pharmacology 102 25498803
2004 Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Human mutation 100 15365989
2016 DJ-1 linked parkinsonism (PARK7) is associated with Lewy body pathology. Brain : a journal of neurology 97 27085187
2017 Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction. Redox biology 96 28954246
2013 MicroRNA-494 reduces DJ-1 expression and exacerbates neurodegeneration. Neurobiology of aging 94 24269020
2013 Parkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo. Proceedings of the National Academy of Sciences of the United States of America 93 23530187
2020 Role of DJ-1 in Immune and Inflammatory Diseases. Frontiers in immunology 90 32612601
2017 DJ-1 deficiency impairs autophagy and reduces alpha-synuclein phagocytosis by microglia. Journal of neurochemistry 90 28921554
2013 SOD1 and DJ-1 converge at Nrf2 pathway: a clue for antioxidant therapeutic potential in neurodegeneration. Oxidative medicine and cellular longevity 90 23983902
2017 DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation. Nature communications 82 29142196
2024 Pathogenesis of DJ-1/PARK7-Mediated Parkinson's Disease. Cells 79 38391909
2017 Recent findings on the physiological function of DJ-1: Beyond Parkinson's disease. Neurobiology of disease 78 28823929
2022 DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia. Scientific reports 73 35190654
2006 Role of DJ-1 in Parkinson's disease. Journal of molecular neuroscience : MN 73 17085780
2013 Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity. The Journal of biological chemistry 68 23792957
2011 Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL. The Journal of biological chemistry 68 21852238
2010 DJ-1, PINK1, and their effects on mitochondrial pathways. Movement disorders : official journal of the Movement Disorder Society 68 20187230
2020 Protective function of DJ-1/PARK7 in lipopolysaccharide and ventilator-induced acute lung injury. Redox biology 66 33246293
2014 Oxidized DJ-1 as a possible biomarker of Parkinson's disease. Journal of clinical biochemistry and nutrition 66 24894116
2017 DJ-1/PARK7: A New Therapeutic Target for Neurodegenerative Disorders. Biological & pharmaceutical bulletin 64 28458339
2021 DJ-1 in neurodegenerative diseases: Pathogenesis and clinical application. Progress in neurobiology 63 34174373
2018 DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis. Cell death & disease 59 30158634
2012 DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling. Nature communications 58 23250426
2008 Expression and role of DJ-1 in leukemia. Biochemical and biophysical research communications 58 18722352
2017 DJ-1/PARK7 Impairs Bacterial Clearance in Sepsis. American journal of respiratory and critical care medicine 57 27735193
2005 Expression of DJ-1 in the adult mouse CNS. Brain research 56 15804505
2004 Detection of Parkin (PARK2) and DJ1 (PARK7) mutations in early-onset Parkinson disease: Parkin mutation frequency depends on ethnic origin of patients. Human mutation 56 15108293
2014 Cross Talk between Two Antioxidant Systems, Thioredoxin and DJ-1: Consequences for Cancer. Oncoscience 55 25593990
2023 PARK7/DJ-1 in microglia: implications in Parkinson's disease and relevance as a therapeutic target. Journal of neuroinflammation 54 37072827
2022 Modulation of signaling pathways by DJ-1: An updated overview. Redox biology 54 35303520
2012 DJ-1 expression modulates astrocyte-mediated protection against neuronal oxidative stress. Journal of molecular neuroscience : MN 54 23065353
2018 6-Hydroxydopamine induces secretion of PARK7/DJ-1 via autophagy-based unconventional secretory pathway. Autophagy 49 30112966
2022 PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing. Nature metabolism 47 35618940
2017 Hexokinases link DJ-1 to the PINK1/parkin pathway. Molecular neurodegeneration 47 28962651
2013 DJ-1 cooperates with PYCR1 in cell protection against oxidative stress. Biochemical and biophysical research communications 45 23743200
2020 DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke. Journal of neuroinflammation 44 32151250
2020 Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression. Journal of clinical medicine 44 32357493
2021 The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson's Disease. Cells 43 33562311
2022 DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons. Journal of neurochemistry 42 35713360
2014 DJ-1 upregulates breast cancer cell invasion by repressing KLF17 expression. British journal of cancer 42 24504364
2013 DJ-1 modulates aggregation and pathogenesis in models of Huntington's disease. Human molecular genetics 40 24070869
2012 DJ-1 regulates mast cell activation and IgE-mediated allergic responses. The Journal of allergy and clinical immunology 40 23182168
2018 DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability at nerve terminals. Proceedings of the National Academy of Sciences of the United States of America 39 29386384
2017 Regulation of Signal Transduction by DJ-1. Advances in experimental medicine and biology 38 29147906
2014 Regulation of the VHL/HIF-1 pathway by DJ-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 24899725
2016 Parkinsonism-associated protein DJ-1 is a bona fide deglycase. Biochemical and biophysical research communications 37 28013050
2015 Differential effect of DJ-1/PARK7 on development of natural and induced regulatory T cells. Scientific reports 35 26634899
2014 Immunostaining of oxidized DJ-1 in human and mouse brains. Journal of neuropathology and experimental neurology 35 24918637
2020 DJ-1 is indispensable for the S-nitrosylation of Parkin, which maintains function of mitochondria. Scientific reports 34 32152416
2017 Structural Biology of the DJ-1 Superfamily. Advances in experimental medicine and biology 34 29147900
2015 PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases. Clinical science (London, England : 1979) 34 26453619
2017 Expression of DJ-1 in Neurodegenerative Disorders. Advances in experimental medicine and biology 33 29147901
2021 DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury. Redox biology 32 33561740
2004 DJ-1 mutations in Parkinson's disease. Journal of neurology, neurosurgery, and psychiatry 31 14707326
2020 Small Substrate or Large? Debate Over the Mechanism of Glycation Adduct Repair by DJ-1. Cell chemical biology 30 32783963
2016 Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson's Disease. Biochemistry 30 26894491
2016 The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte. Biochemical and biophysical research communications 30 26995087
2014 DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis. The Biochemical journal 30 24947010
2012 DJ-1/park7 protects against neointimal formation via the inhibition of vascular smooth muscle cell growth. Cardiovascular research 30 23230227
2021 DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing Mitophagy. Cellular and molecular gastroenterology and hepatology 29 33766785
2020 Role of DJ-1 in Modulating Glycative Stress in Heart Failure. Journal of the American Heart Association 29 32067589
2017 Transcriptional Regulation of DJ-1. Advances in experimental medicine and biology 29 29147905
2017 DJ-1 as a Biomarker of Parkinson's Disease. Advances in experimental medicine and biology 29 29147908
2014 The role of DJ-1 in the oxidative stress cell death cascade after stroke. Neural regeneration research 29 25317153
2013 DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase. Cardiovascular research 29 24323315
2006 Distribution of DJ-1, Parkinson's disease-related protein PARK7, and its alteration in 6-hydroxydopamine-treated hemiparkinsonian rat brain. Journal of pharmacological sciences 29 17038803
2007 DJ-1 (PARK7) is associated with 3R and 4R tau neuronal and glial inclusions in neurodegenerative disorders. Neurobiology of disease 27 17719794
2017 Expression of DJ-1 in Cancer Cells: Its Correlation with Clinical Significance. Advances in experimental medicine and biology 26 29147902
2013 DJ-1 ameliorates ischemic cell death in vitro possibly via mitochondrial pathway. Neurobiology of disease 26 24060818
2020 DJ-1 (Park7) affects the gut microbiome, metabolites and the development of innate lymphoid cells (ILCs). Scientific reports 25 32999308
2013 Cheek cell-derived α-synuclein and DJ-1 do not differentiate Parkinson's disease from control. Neurobiology of aging 25 24041968
2010 α-Synuclein and DJ-1 as potential biological fluid biomarkers for Parkinson's Disease. International journal of molecular sciences 25 21151436
2017 DJ-1 as a Therapeutic Target Against Cancer. Advances in experimental medicine and biology 24 29147911
2017 Intracellular metal binding and redox behavior of human DJ-1. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 24 29218631
2022 PARK7/DJ-1 as a Therapeutic Target in Gut-Brain Axis Diseases. International journal of molecular sciences 22 35743072
2021 Extracellular DJ-1 induces sterile inflammation in the ischemic brain. PLoS biology 22 34014921
2017 DJ-1 activates autophagy in the repression of cardiac hypertrophy. Archives of biochemistry and biophysics 22 28941803
2014 DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor. Atherosclerosis 21 24953490
2011 DJ-1 mediates paraquat-induced dopaminergic neuronal cell death. Toxicology letters 21 21300143
2022 Moving beyond the Tip of the Iceberg: DJ-1 Implications in Cancer Metabolism. Cells 20 35563738
2021 Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology. Molecules (Basel, Switzerland) 20 34206441
2015 DJ-1 mutation decreases astroglial release of inflammatory mediators. Neurotoxicology 20 26691871

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