Affinage

PARK7

Parkinson disease protein 7 · UniProt Q99497

Length
189 aa
Mass
19.9 kDa
Annotated
2026-04-29
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DJ-1 (PARK7) is a redox-sensitive homodimeric protein that functions as a multifaceted cytoprotective factor, integrating oxidative stress sensing, mitochondrial quality control, proteasome regulation, and transcriptional modulation to maintain cellular homeostasis, particularly in neurons. Its conserved Cys106 residue undergoes selective oxidation to sulfinic acid in living cells, serving as the primary redox sensor that governs DJ-1's interactions with mitochondrial Bcl-XL (stabilizing it against ubiquitin-mediated degradation), p53 (sequestering it from low-affinity promoters to suppress pro-apoptotic gene expression), and PTEN (via transnitrosylation to inhibit phosphatase activity), while also enabling ROS scavenging through self-oxidation and glyoxalase activity toward methylglyoxal (PMID:29218631, PMID:21852238, PMID:23149933, PMID:25378175, PMID:14749723, PMID:25283443). DJ-1 operates within the PINK1/parkin mitophagy axis as an essential downstream effector that enables optineurin recruitment to depolarized mitochondria, directly binds complex I subunits to maintain oxidative phosphorylation, inhibits the 20S proteasome to rescue partially unfolded substrates including α-synuclein, and regulates NADPH oxidase-dependent ROS production in macrophages by disrupting the p47phox–Nox2 complex (PMID:36039535, PMID:19822128, PMID:25833141, PMID:27735193). Loss-of-function mutations in PARK7 cause autosomal recessive early-onset parkinsonism (PMID:12446870).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Identifying DJ-1 as a Parkinson's disease gene established that its function is essential for neuronal survival but left the molecular mechanism entirely unknown.

    Evidence Genetic linkage analysis and mutation screening in consanguineous PD families

    PMID:12446870

    Open questions at the time
    • No biochemical function was known
    • Mechanism of neurodegeneration upon DJ-1 loss was uncharacterized
    • Whether DJ-1 acted cell-autonomously was unknown
  2. 2004 High

    Demonstrating that DJ-1 eliminates H₂O₂ through self-oxidation provided the first biochemical activity and linked DJ-1 directly to oxidative stress defense.

    Evidence In vitro H₂O₂ elimination assay and siRNA knockdown in SH-SY5Y neuroblastoma cells

    PMID:14749723

    Open questions at the time
    • The specific oxidizable residue was not yet identified
    • Whether self-oxidation was the primary protective mechanism in vivo was unclear
    • Relationship to other antioxidant systems was not addressed
  3. 2006 High

    Discovery of K130 sumoylation as essential for all tested DJ-1 functions, and that the PD-linked L166P mutant is aberrantly sumoylated and degraded, connected post-translational modification to disease pathogenesis.

    Evidence Co-immunoprecipitation with SUMO E3 ligases, K130 mutagenesis, proteasome inhibitor rescue of L166P

    PMID:15976810

    Open questions at the time
    • How sumoylation mechanistically enables DJ-1 function was not resolved
    • Whether sumoylation regulates specific subsets of DJ-1 activity remained unclear
  4. 2007 High

    Showing that DJ-1 binds p53 and represses its transcriptional activity on pro-apoptotic targets like Bax revealed a transcriptional regulatory mechanism for DJ-1-mediated cytoprotection.

    Evidence Co-immunoprecipitation in vitro/in vivo, Bax expression and caspase activation upon DJ-1 overexpression/knockdown

    PMID:18042550

    Open questions at the time
    • The oxidation dependence of the DJ-1–p53 interaction was not yet established
    • Whether DJ-1 regulates all or only select p53 targets was unknown
  5. 2009 Medium

    Identification of DJ-1 binding to complex I subunits NDUFA4 and ND1 with reduced complex I activity upon DJ-1 loss established a direct mitochondrial electron transport chain maintenance role.

    Evidence Co-immunoprecipitation, co-localization, complex I activity assay in knockdown cells

    PMID:19822128

    Open questions at the time
    • Whether DJ-1 is a stable complex I-associated factor or a transient regulator was unclear
    • The mechanism by which DJ-1 maintains complex I activity was not defined
    • Not independently replicated at time of publication
  6. 2010 High

    Finding that DJ-1 inhibits the deubiquitinase Cezanne to promote NF-κB signaling expanded DJ-1's role beyond antioxidant defense into inflammatory and survival signaling.

    Evidence MS interactome, reciprocal co-IP of endogenous proteins, DUB activity assay, NF-κB reporter in Park7⁻/⁻ cells

    PMID:21097510

    Open questions at the time
    • Physiological context (which cell types and stimuli) for DJ-1–Cezanne axis was not fully defined
    • Whether this interaction is redox-regulated was not tested
  7. 2011 High

    Demonstrating that oxidized DJ-1 stabilizes mitochondrial Bcl-XL by inhibiting its ubiquitination in a C106-dependent manner provided a direct anti-apoptotic mechanism at mitochondria.

    Evidence Reciprocal co-IP, C106A mutagenesis, ubiquitination assay, knockdown with apoptosis readouts

    PMID:21852238

    Open questions at the time
    • The E3 ligase responsible for Bcl-XL ubiquitination antagonized by DJ-1 was not identified
    • Whether this mechanism operates in dopaminergic neurons in vivo was not shown
  8. 2012 High

    A series of 2012 studies collectively resolved that DJ-1 selectively sequesters p53 from low-affinity promoters via C106 oxidation-dependent binding, modulates PINK1/parkin-dependent mitophagy in neurons as a C106-dependent ROS buffer, and regulates dendritic morphology through β-tubulin III/HIF-1α, revealing context-specific mechanistic outputs of the same redox sensor.

    Evidence ChIP + promoter reporters + C106S mutagenesis for p53 selectivity; live-cell imaging + DJ-1 KO neuronal rescue for mitophagy; Golgi-Cox impregnation in DJ-1 KO mice for dendritic morphology

    PMID:22609282 PMID:22872702 PMID:22892098 PMID:23149933

    Open questions at the time
    • Whether DJ-1 promotes or restrains mitophagy appeared contradictory between studies
    • The L166P mutant's gain-of-function at Bcl-XL (PMID:22892098) was from a single lab
    • Mechanism linking DJ-1 to HIF-1α regulation of β-tubulin III was not fully delineated
  9. 2013 Medium

    Discovery that DJ-1 directly activates PYCR1 enzymatic activity in mitochondria placed DJ-1 in the proline biosynthesis pathway as an oxidative stress defense mechanism.

    Evidence Co-IP in vivo/in vitro, PYCR1 activity assay, epistasis via double knockdown

    PMID:23743200

    Open questions at the time
    • Single-lab finding not independently replicated
    • Whether PYCR1 activation is C106-dependent was not tested
    • Quantitative contribution of this pathway to DJ-1-mediated neuroprotection was unknown
  10. 2014 High

    Structural resolution of DJ-1's S-nitrosylation at C106 and its transnitrosylase activity toward PTEN, plus crystallographic capture of the glyoxalase hemithioacetal intermediate, defined two distinct catalytic mechanisms centered on the same active-site cysteine.

    Evidence X-ray crystallography of SNO-DJ-1 and glyoxylate-bound DJ-1, biotin-switch assay, PTEN phosphatase activity assay, mass spectrometry

    PMID:25283443 PMID:25378175

    Open questions at the time
    • Whether transnitrosylation of PTEN occurs in dopaminergic neurons in vivo was not demonstrated
    • The physiological relevance of glyoxalase vs. deglycase activity remained debated
  11. 2015 High

    Demonstrating that DJ-1 physically inhibits the 20S proteasome and rescues partially unfolded proteins including α-synuclein from degradation revealed an unexpected proteostasis role that directly intersects with PD pathology.

    Evidence Co-IP, in vitro proteasome activity assays, mass spectrometry, substrate stabilization by Western blot

    PMID:25833141

    Open questions at the time
    • Whether proteasome inhibition is beneficial or detrimental in the context of α-synuclein aggregation was not resolved
    • In vivo relevance in dopaminergic neurons was not shown
  12. 2016 Medium

    Identification of DJ-1 glutathionylation at two cysteines regulated by Grx1 added a new layer of redox-dependent post-translational control over DJ-1 protein levels.

    Evidence Grx1 KO mice, recombinant deglutathionylation assay, mass spectrometry, C. elegans rescue

    PMID:26894491

    Open questions at the time
    • Which cysteines are glutathionylated and their functional consequences were not fully mapped
    • Cross-species validation in C. elegans may not reflect mammalian physiology
  13. 2017 High

    Multiple 2017 studies extended DJ-1's roles beyond neurons: DJ-1 inhibits NADPH oxidase in macrophages via p47phox binding, promotes PTEN degradation via Mib2 to regulate brown fat thermogenesis, controls muscle metabolism through mitochondrial uncoupling/AMPK, regulates VMAT2 transcription for dopamine vesicular storage, and maintains hexokinase 1 mitochondrial association for PINK1/parkin signaling.

    Evidence DJ-1 KO mice metabolic phenotyping; co-IP of DJ-1 with p47phox, Mib2, and PTEN; ChIP at VMAT2 promoter; proteomic screen in DJ-1 KO brains

    PMID:22887838 PMID:26077864 PMID:27735193 PMID:28224045 PMID:28962651

    Open questions at the time
    • Whether the p47phox and Mib2 interactions are redox-regulated was not tested
    • The hexokinase–DJ-1 connection was from a single lab with indirect evidence
    • Integration of these tissue-specific functions into a unified model was lacking
  14. 2017 High

    In-cell NMR confirmed that C106 is selectively and completely oxidized to sulfinic acid in living cells, validating it as a bona fide intracellular redox sensor and establishing that DJ-1 is largely monomeric/free from stable complexes under basal conditions.

    Evidence In-cell NMR spectroscopy in living human cells with oxidative stress treatment

    PMID:29218631

    Open questions at the time
    • The NMR observation of free DJ-1 under basal conditions seems to contradict numerous interaction studies — conditions of engagement were not reconciled
    • Metal binding under stress conditions was not fully explored
  15. 2018 Medium

    Mutation-specific analysis showed that M26I enhances SUMO-1 interaction and mitophagy while D149A disrupts DJBP/EFCAB6 binding and calcium dynamics, demonstrating that different PD mutations impair distinct DJ-1 functional modules.

    Evidence Co-IP of mutant DJ-1 with SUMO-1 and DJBP, mitophagy flux, Ca²⁺ imaging, ROS measurement

    PMID:29599708

    Open questions at the time
    • Single-lab study with overexpressed mutants
    • Whether DJBP interaction is physiologically relevant in neurons was not shown
    • Endogenous-level validation of mutant-specific effects was lacking
  16. 2020 Medium

    Defining the C-terminal residues and L187 as essential for homodimerization, methylglyoxal detoxification, and ferroptosis suppression linked DJ-1 quaternary structure to two specific cytoprotective outputs.

    Evidence Co-IP with tagged constructs, deletion/point mutagenesis, MGO assay, ferroptosis viability in DJ-1⁻/⁻ MEFs

    PMID:33024240

    Open questions at the time
    • Ferroptosis suppression mechanism was not molecularly defined beyond dimerization requirement
    • Whether dimerization-deficient DJ-1 retains any function in vivo was not tested
  17. 2022 High

    Three 2022 studies resolved key outstanding questions: DJ-1 acts downstream of PINK1/parkin to recruit optineurin for mitophagy (independent of C106 oxidation), promotes PDH activity by binding PDHB to support Treg cell metabolism, and inhibits PSMB10 proteasome subunit to stabilize ATRAP in cardiac hypertrophy; kinetic modeling established DJ-1 as a glyoxalase rather than a deglycase.

    Evidence PARK7-mutant iPSC neurons + epistasis for mitophagy; co-IP of DJ-1–PDHB + Park7 KO Treg phenotyping; co-IP of DJ-1–PSMB10 + cardiac models; isotope-dilution MS kinetics for glyoxalase activity

    PMID:35618940 PMID:35713360 PMID:36039535 PMID:36509316

    Open questions at the time
    • Optineurin recruitment mechanism (direct vs. indirect) was not determined
    • How C106-independent mitophagy function relates to C106-dependent antioxidant functions is not integrated
    • Whether DJ-1's PDH-regulatory role extends beyond Treg cells was not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified model integrating DJ-1's redox-dependent and redox-independent functions across cell types, and resolving contradictions between its roles as mitophagy promoter vs. ROS buffer restraining excessive mitophagy, remains to be established.
  • No structural basis for how DJ-1 recruits optineurin to mitochondria
  • The relative physiological importance of glyoxalase, transnitrosylase, proteasome inhibitor, and ROS scavenger activities is undefined
  • Whether extracellular DAMP function of DJ-1 contributes to PD neuroinflammation in patients is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0016491 oxidoreductase activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005739 mitochondrion 5 GO:0005634 nucleus 2 GO:0005576 extracellular region 1 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
BCL2L1CYBBNCF1OPTNPDHBPTENPYCR1TP53
Complex memberships
20S proteasome (as inhibitor, not subunit)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Loss-of-function mutations in DJ-1 (PARK7) cause autosomal recessive early-onset parkinsonism, establishing that DJ-1 function is required for neuronal maintenance. Genetic linkage analysis and mutation identification in familial PD cohorts Science High 12446870
2004 DJ-1 eliminates hydrogen peroxide in vitro by oxidizing itself (self-oxidation), and DJ-1 knockdown renders neuroblastoma cells susceptible to H2O2-, MPP+-, and 6-OHDA-induced cell death; loss of oxidized DJ-1 forms correlates with susceptibility. In vitro H2O2 elimination assay; siRNA knockdown in SH-SY5Y cells with cell viability readouts EMBO reports High 14749723
2006 DJ-1 is sumoylated at lysine 130 (K130) by SUMO E3 ligases PIASxα or PIASy; K130 mutation abrogates all DJ-1 functions including transformation, cell growth, and anti-apoptosis; the PD-linked L166P mutant is improperly sumoylated, becomes insoluble, partly localizes to mitochondria, and is degraded by the proteasome. Co-immunoprecipitation, site-directed mutagenesis, subcellular fractionation, proteasome inhibitor rescue Cell death and differentiation High 15976810
2007 DJ-1 interacts with p53 in vitro and in vivo, and overexpression of DJ-1 decreases Bax expression and inhibits caspase activation by repressing p53 transcriptional activity; DJ-1 knockdown increases Bax and caspase-3 activation upon UV exposure. Co-immunoprecipitation (in vitro and in vivo), overexpression/knockdown with Western blot and luciferase reporter assays The Journal of biological chemistry High 18042550
2009 DJ-1 directly binds to NDUFA4 and ND1 (nuclear- and mitochondrial-encoded subunits of mitochondrial complex I), co-localizes with complex I, and complex I activity is reduced in DJ-1-knockdown cells. Co-immunoprecipitation, co-localization by immunofluorescence, complex I activity assay in knockdown cells Biochemical and biophysical research communications Medium 19822128
2011 Oxidized DJ-1 (C106 oxidation-dependent) interacts with mitochondrial Bcl-XL; DJ-1 stabilizes Bcl-XL by inhibiting its ubiquitination and proteasomal degradation in response to UVB irradiation; DJ-1 knockdown increases Bcl-XL ubiquitination, elevates mitochondrial Bax, and activates caspase-3. Co-immunoprecipitation, site-directed mutagenesis (C106A), ubiquitination assay, knockdown with apoptosis readouts The Journal of biological chemistry High 21852238
2012 Oxidized DJ-1 binds to the DNA-binding region of p53 in an oxidation-of-C106-dependent manner, sequestering p53 from promoters with low p53 DNA-binding affinity (e.g., DUSP1) but not from high-affinity sites (e.g., p21), thereby differentially regulating p53 target gene expression and activating ERK to decrease apoptosis. Co-immunoprecipitation, ChIP, promoter reporter assays, site-directed mutagenesis (C106S), DJ-1 knockout cells Molecular and cellular biology High 23149933
2012 ROS-dependent Parkin translocation to damaged mitochondria occurs in neurons; loss of DJ-1 results in increased stress-induced Parkin recruitment and increased mitophagy; expression of wild-type but not C106-mutant DJ-1 rescues this effect; DJ-1 levels increase at mitochondria following oxidative damage in a Parkin/PINK1-dependent manner. Live-cell imaging, fluorescence microscopy, subcellular fractionation, DJ-1 KO neurons, site-directed mutagenesis (C106) Human molecular genetics High 22872702
2014 DJ-1 is S-nitrosylated at Cys106 (forming SNO-DJ-1), and then transnitrosylates PTEN by transferring the NO group, inhibiting PTEN phosphatase activity and promoting cell survival; X-ray crystallography and site-directed mutagenesis confirm Cys106 as the site of S-nitrosylation. X-ray crystallography, site-directed mutagenesis, biotin-switch assay for S-nitrosylation, PTEN phosphatase activity assay, mass spectrometry The Journal of neuroscience High 25378175
2015 DJ-1 physically binds the 20S proteasome and inhibits its activity, rescuing partially unfolded proteins (including α-synuclein and p53) from degradation; under oxidative stress, DJ-1 also participates in Nrf2-dependent upregulation of the 20S proteasome and its regulator NQO1. Co-immunoprecipitation, in vitro proteasome activity assays, mass spectrometry, Western blot for substrate levels Nature communications High 25833141
2010 DJ-1 interacts with Cezanne (OTUD7B), a deubiquitinating enzyme that negatively regulates NF-κB; DJ-1 inhibits Cezanne's deubiquitinating activity, enhancing NF-κB nuclear translocation and cell survival; interaction maps to the N-terminal 70 residues of DJ-1. Mass spectrometry interactome, co-immunoprecipitation of endogenous proteins, deubiquitinase activity assay, NF-κB reporter assay, Park7-/- primary cells The Journal of biological chemistry High 21097510
2012 DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability; familial mutants M26I, E64D, and L166P cannot rescue defective endocytosis in DJ-1 KO neurons; the defect may be attributable to altered membrane cholesterol levels. Live imaging (pHluorin-based endocytosis assay), DJ-1 KO neurons, rescue with WT and mutant DJ-1, membrane cholesterol measurement PNAS High 29386384
2013 DJ-1 cooperates with PYCR1 (pyrroline-5-carboxylate reductase 1) in mitochondria to protect cells against oxidative stress; DJ-1 directly binds PYCR1 in vivo and in vitro and enhances its enzymatic activity; double knockdown shows no additive effect, placing them in the same pathway. Co-immunoprecipitation (in vivo and in vitro), enzymatic activity assay of PYCR1, co-localization, siRNA knockdown with cell viability Biochemical and biophysical research communications Medium 23743200
2017 DJ-1 inhibits ROS production in macrophages by binding to p47phox, a critical component of the NADPH oxidase complex, disrupting the complex and facilitating Nox2 (gp91phox) ubiquitination and degradation; DJ-1 deficiency enhances phagocytosis and bactericidal activity. Co-immunoprecipitation, ubiquitination assay, ROS measurement, DJ-1-/- macrophages, adoptive transfer rescue experiment American journal of respiratory and critical care medicine High 27735193
2022 DJ-1 is essential downstream of PINK1 and parkin for mitophagy; loss of DJ-1 blocks recruitment of the selective autophagy receptor optineurin to depolarized mitochondria without affecting PINK1 or parkin activation; endogenous DJ-1 translocates to depolarized mitochondria near optineurin in a PINK1/parkin-dependent manner; C106 oxidation is not required for this translocation. Human fibroblasts and iPSC-derived neurons with PARK7 mutations, mitophagy flux assay, immunofluorescence co-localization, site-directed mutagenesis (C106), epistasis by sequential KO Brain High 36039535
2022 DJ-1 binds to PDHB (PDHE1-β), inhibiting phosphorylation of PDHE1-α (PDHA), thereby promoting pyruvate dehydrogenase (PDH) activity and oxidative phosphorylation in CD4+ regulatory T cells (Treg cells); DJ-1 deletion impairs Treg survival and homeostatic proliferation. Co-immunoprecipitation (DJ-1 and PDHB), PDH activity assay, Park7 KO mice with Treg functional readouts, metabolomics Nature metabolism High 35618940
2017 DJ-1 deficiency in skeletal muscle results in mitochondrial uncoupling via ROS that activates AMP-activated protein kinase (AMPK), triggering Warburg-like metabolic reprogramming; DJ-1 KO mice show higher energy expenditure and are protected from obesity and insulin resistance. DJ-1 KO mice, mitochondrial respiration assays, AMPK activation measurement, metabolic phenotyping Nature communications High 26077864
2021 Extracellular DJ-1 released from necrotic neurons acts as a damage-associated molecular pattern (DAMP) activating Toll-like receptor 2 (TLR2) and TLR4 in infiltrating myeloid cells via a specific peptide in the αG and αH helices of DJ-1, inducing sterile neuroinflammation after ischemic stroke. Recombinant protein stimulation of macrophages/dendritic cells, TLR2/TLR4 co-immunoprecipitation, neutralizing antibody, DJ-1 KO mouse stroke model with cytokine readouts PLoS biology High 34014921
2017 DJ-1 promotes PTEN proteasomal degradation via the E3 ligase Mib2, leading to Akt activation and inhibition of FoxO1-dependent Ucp1 expression in brown adipose tissue, thereby regulating energy homeostasis. Co-immunoprecipitation (DJ-1 with Mib2 and PTEN), ubiquitination assay, DJ-1 KO and transgenic mice, Akt1 KO rescue experiment Cell discovery High 28224045
2017 DJ-1 deficiency in mouse and rat brain causes age-dependent accumulation of hexokinase 1 in the cytosol away from mitochondria and activation of the polyol pathway; hexokinase dissociation from mitochondria inhibits the PINK1/parkin mitochondrial quality control pathway, linking DJ-1 to hexokinase-PINK1/parkin axis. Proteomic screens in DJ-1 KO rodent brains, targeted biochemical validation, hexokinase-mitochondria dissociation peptide assay, AKT inhibitor epistasis in cells Molecular neurodegeneration Medium 28962651
2016 DJ-1 is glutathionylated at two distinct cysteine sites; Glutaredoxin 1 (Grx1) de-glutathionylates DJ-1 in vivo and regulates DJ-1 protein levels; Grx1 KO mice show decreased DJ-1 protein; overexpression of DJ-1 partially compensates for loss of Grx1 in a C. elegans PD model. Grx1 KO mice (in vivo), recombinant protein glutathionylation assay, mass spectrometry of glutathionylation sites, C. elegans genetic model Biochemistry Medium 26894491
2018 The DJ-1 M26I mutant influences DJ-1 interaction with SUMO-1, enhancing mitophagy and increasing cellular susceptibility to dopamine toxicity; the DJ-1 D149A mutant impairs Ca2+ dynamics and free radical homeostasis by disrupting interaction with DJ-1-binding protein (DJBP/EFCAB6), without affecting mitophagy. Co-immunoprecipitation of DJ-1 with SUMO-1 and DJBP, mitophagy flux assay, Ca2+ imaging, ROS measurement, mutation-specific analysis Frontiers in molecular neuroscience Medium 29599708
2014 DJ-1 interacts with RACK1, increases RACK1 dimerization and protein stability; the DJ-1-RACK1 complex protects cortical neurons from H2O2-induced apoptosis; this interaction is disrupted by H2O2 or MPP+ treatment. Co-immunoprecipitation, overexpression and knockdown in cortical neurons, cell viability assay, protein stability analysis The Biochemical journal Medium 24947010
2017 DJ-1 protects dopaminergic neurons from dopamine toxicity and upregulates VMAT2 expression transcriptionally; chromatin immunoprecipitation confirms DJ-1 regulation of VMAT2 promoter; DJ-1 knockdown reduces VMAT2 expression and dopamine vesicular sequestration. ChIP assay, VMAT2 expression analysis, overexpression/knockdown, 6-OHDA mouse model, DJ-1 KO mice The journals of gerontology. Series A Medium 22887838
2012 L166P mutant DJ-1 preferentially localizes to mitochondria, binds Bcl-XL more strongly than WT DJ-1, and dissociates Bax from Bcl-XL under UVB irradiation, promoting mitochondrial Bax enrichment and apoptosis; WT DJ-1 does not dissociate Bax from Bcl-XL. Co-immunoprecipitation, subcellular fractionation, apoptosis assays (caspase-3, PARP), comparison of WT and L166P mutant Molecular neurodegeneration Medium 22892098
2014 DJ-1 crystal structure with glyoxylate (analog of methylglyoxal) forming a hemithioacetal at the active-site Cys reveals the catalytic mechanism of DJ-1 glyoxalase activity; the presence or absence of a His residue alongside the conserved Cys and Glu determines stereospecificity of lactate production. X-ray crystallography of hemithioacetal-bound hDJ-1, deuteration experiments, molecular modeling The FEBS journal Medium 25283443
2020 DJ-1 C-terminal residues (last 3 amino acids) and hydrophobic L187 are required for homodimerization; deletion of the C-terminus (ΔC3) or L187E mutation abolishes homodimerization, methylglyoxal detoxification activity, and suppression of erastin-triggered ferroptosis. Co-immunoprecipitation with Flag- and Myc-tagged DJ-1, deletion and point mutagenesis, MGO detoxification assay, ferroptosis cell viability assay in DJ-1-/- MEFs Acta pharmacologica Sinica Medium 33024240
2022 DJ-1 directly interacts with proteasome subunit PSMB10 and inhibits its activity, preventing ubiquitin-mediated degradation of ATRAP (AT1R-associated protein), thereby suppressing AT1R-mediated cardiac hypertrophy signaling. Quantitative proteomics, co-immunoprecipitation, proteasome activity assay, ubiquitination assay, cardiac hypertrophy models in vitro and in vivo Pharmacological research Medium 36509316
2012 DJ-1 deficiency perturbs microtubule dynamics by downregulating β-tubulin III via a HIF-1α pathway, leading to reduced dendritic complexity and loss of dendritic spines in striatal medium spiny neurons of DJ-1-deficient mice. DJ-1 knockdown in neuroblastoma cells and DJ-1 KO mice, β-tubulin III Western blot, Golgi-Cox impregnation for dendritic morphology, microtubule dynamics assay Neurobiology of aging Medium 22609282
2017 In-cell NMR shows that intracellular DJ-1 is free from interactions with other cellular components; C106 is selectively and completely oxidized to sulfinic acid upon oxidative treatment in living cells, confirming its role as a redox sensor in vivo; DJ-1 does not bind zinc or copper intracellularly under normal conditions. In-cell NMR spectroscopy in living human cells, oxidative stress treatment, metal supplementation experiments Journal of biological inorganic chemistry High 29218631
2022 DJ-1 is not a true deglycase; kinetic modeling supports DJ-1 acting as a glyoxalase on hemithioacetal small-molecule substrates rather than deglycating protein adducts; DJ-1 modestly reduces some irreversible glycation products in neuronal cells and mouse brain, but does not improve cell viability under exogenous methylglyoxal. In vitro kinetic assays with isotope-dilution mass spectrometry, computational kinetic modeling, primary and cultured neuronal cells, whole mouse brain biochemistry Journal of neurochemistry Medium 35713360

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science (New York, N.Y.) 2194 12446870
2004 DJ-1 has a role in antioxidative stress to prevent cell death. EMBO reports 718 14749723
2006 Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. The Journal of biological chemistry 396 16517609
2013 Neuroprotective function of DJ-1 in Parkinson's disease. Oxidative medicine and cellular longevity 297 23766857
2011 The role of cysteine oxidation in DJ-1 function and dysfunction. Antioxidants & redox signaling 264 20812780
2007 Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. Current opinion in neurobiology 208 17499497
2007 DJ-1 decreases Bax expression through repressing p53 transcriptional activity. The Journal of biological chemistry 205 18042550
2019 Role of DJ-1 in the mechanism of pathogenesis of Parkinson's disease. Journal of bioenergetics and biomembranes 203 31054074
2012 ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Human molecular genetics 177 22872702
2009 DJ-1 binds to mitochondrial complex I and maintains its activity. Biochemical and biophysical research communications 170 19822128
2006 Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities. Cell death and differentiation 148 15976810
2011 DJ-1 regulation of mitochondrial function and autophagy through oxidative stress. Autophagy 138 21317550
2005 DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Annals of neurology 134 16240358
2019 DJ-1 in Parkinson's Disease: Clinical Insights and Therapeutic Perspectives. Journal of clinical medicine 132 31484320
2022 DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy. Brain : a journal of neurology 115 36039535
2008 Oxidative insults induce DJ-1 upregulation and redistribution: implications for neuroprotection. Neurotoxicology 110 18377993
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 100 25498803
2005 PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. European journal of human genetics : EJHG 100 15970950
2004 Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Human mutation 100 15365989
2017 Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction. Redox biology 95 28954246
2010 Keap1-Nrf2 activation in the presence and absence of DJ-1. The European journal of neuroscience 95 20377612
2016 DJ-1 linked parkinsonism (PARK7) is associated with Lewy body pathology. Brain : a journal of neurology 93 27085187
2017 DJ-1 deficiency impairs autophagy and reduces alpha-synuclein phagocytosis by microglia. Journal of neurochemistry 90 28921554
2014 Transnitrosylation from DJ-1 to PTEN attenuates neuronal cell death in parkinson's disease models. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 25378175
2014 Increased DJ-1 in urine exosome of Korean males with Parkinson's disease. BioMed research international 89 25478574
2020 Role of DJ-1 in Immune and Inflammatory Diseases. Frontiers in immunology 88 32612601
2012 Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner. Molecular and cellular biology 85 23149933
2012 DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. Carcinogenesis 84 22223849
2017 Recent findings on the physiological function of DJ-1: Beyond Parkinson's disease. Neurobiology of disease 76 28823929
2015 DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice. Nature communications 73 26077864
2007 Secretion of DJ-1 into the serum of patients with Parkinson's disease. Neuroscience letters 73 18162323
2022 DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia. Scientific reports 72 35190654
2006 Role of DJ-1 in Parkinson's disease. Journal of molecular neuroscience : MN 72 17085780
2012 Decline in DJ-1 and decreased nuclear translocation of Nrf2 in Fuchs endothelial corneal dystrophy. Investigative ophthalmology & visual science 70 22836768
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
2014 Oxidized DJ-1 as a possible biomarker of Parkinson's disease. Journal of clinical biochemistry and nutrition 66 24894116
2024 Pathogenesis of DJ-1/PARK7-Mediated Parkinson's Disease. Cells 64 38391909
2017 DJ-1/PARK7: A New Therapeutic Target for Neurodegenerative Disorders. Biological & pharmaceutical bulletin 63 28458339
2021 DJ-1 in neurodegenerative diseases: Pathogenesis and clinical application. Progress in neurobiology 61 34174373
2010 DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB. The Journal of biological chemistry 57 21097510
2017 The Multifaceted Roles of DJ-1 as an Antioxidant. Advances in experimental medicine and biology 56 29147904
2017 DJ-1/PARK7 Impairs Bacterial Clearance in Sepsis. American journal of respiratory and critical care medicine 55 27735193
2014 Cross Talk between Two Antioxidant Systems, Thioredoxin and DJ-1: Consequences for Cancer. Oncoscience 55 25593990
2005 Expression of DJ-1 in the adult mouse CNS. Brain research 55 15804505
2006 Zebrafish DJ-1 is evolutionarily conserved and expressed in dopaminergic neurons. Brain research 54 16942755
2022 Modulation of signaling pathways by DJ-1: An updated overview. Redox biology 52 35303520
2015 Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice. Experimental eye research 51 26215528
2023 PARK7/DJ-1 in microglia: implications in Parkinson's disease and relevance as a therapeutic target. Journal of neuroinflammation 49 37072827
2017 Hexokinases link DJ-1 to the PINK1/parkin pathway. Molecular neurodegeneration 46 28962651
2016 Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification. The Journal of biological chemistry 46 27903648
2022 PARK7/DJ-1 promotes pyruvate dehydrogenase activity and maintains Treg homeostasis during ageing. Nature metabolism 44 35618940
2020 Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression. Journal of clinical medicine 44 32357493
2017 DJ-1 maintains energy and glucose homeostasis by regulating the function of brown adipose tissue. Cell discovery 43 28224045
2013 DJ-1 cooperates with PYCR1 in cell protection against oxidative stress. Biochemical and biophysical research communications 43 23743200
2004 Causes of Parkinson's disease: genetics of DJ-1. Cell and tissue research 42 15503154
2021 The Role of DJ-1 in Cellular Metabolism and Pathophysiological Implications for Parkinson's Disease. Cells 41 33562311
2007 Destabilization of DJ-1 by familial substitution and oxidative modifications: implications for Parkinson's disease. Biochemistry 41 17451229
2022 DJ-1 is not a deglycase and makes a modest contribution to cellular defense against methylglyoxal damage in neurons. Journal of neurochemistry 40 35713360
2018 Effect of DJ-1 on the neuroprotection of astrocytes subjected to cerebral ischemia/reperfusion injury. Journal of molecular medicine (Berlin, Germany) 40 30506316
2016 DJ-1 modulates mitochondrial response to oxidative stress: clues from a novel diagnosis of PARK7. Clinical genetics 40 27460976
2012 DJ-1 protects against dopamine toxicity: implications for Parkinson's disease and aging. The journals of gerontology. Series A, Biological sciences and medical sciences 40 22887838
2013 DJ-1 modulates aggregation and pathogenesis in models of Huntington's disease. Human molecular genetics 39 24070869
2011 Down-regulation of DJ-1 protein in the ejaculated spermatozoa from Chinese asthenozoospermia patients. Fertility and sterility 39 21575935
2017 Regulation of Signal Transduction by DJ-1. Advances in experimental medicine and biology 38 29147906
2014 Stereospecific mechanism of DJ-1 glyoxalases inferred from their hemithioacetal-containing crystal structures. The FEBS journal 38 25283443
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 37 29386384
2016 Parkinsonism-associated protein DJ-1 is a bona fide deglycase. Biochemical and biophysical research communications 37 28013050
2014 Immunostaining of oxidized DJ-1 in human and mouse brains. Journal of neuropathology and experimental neurology 35 24918637
2011 Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7. Journal of pharmacological sciences 35 22041943
2017 Structural Biology of the DJ-1 Superfamily. Advances in experimental medicine and biology 34 29147900
2017 Expression of DJ-1 in Neurodegenerative Disorders. Advances in experimental medicine and biology 33 29147901
2011 DJ-1 may contribute to metastasis of non-small cell lung cancer. Molecular biology reports 33 21670963
2015 The DJ-1 superfamily member Hsp31 repairs proteins from glycation by methylglyoxal and glyoxal. Biochemical and biophysical research communications 32 26102038
2009 Protection against oxidative stress-induced neurodegeneration by a modulator for DJ-1, the wild-type of familial Parkinson's disease-linked PARK7. Journal of pharmacological sciences 31 19276614
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
2015 DJ-1 knockout augments disease severity and shortens survival in a mouse model of ALS. PloS one 30 25822630
2014 DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis. The Biochemical journal 30 24947010
2012 L166P mutant DJ-1 promotes cell death by dissociating Bax from mitochondrial Bcl-XL. Molecular neurodegeneration 30 22892098
2010 DJ-1 forms complexes with mutant SOD1 and ameliorates its toxicity. Journal of neurochemistry 29 20202083
2020 Role of DJ-1 in Modulating Glycative Stress in Heart Failure. Journal of the American Heart Association 28 32067589
2014 The role of DJ-1 in the oxidative stress cell death cascade after stroke. Neural regeneration research 28 25317153
2018 Distinct Mechanisms of Pathogenic DJ-1 Mutations in Mitochondrial Quality Control. Frontiers in molecular neuroscience 27 29599708
2017 Transcriptional Regulation of DJ-1. Advances in experimental medicine and biology 27 29147905
2012 High levels of DJ-1 protein in nipple fluid of patients with breast cancer. Cancer science 27 22404125
2003 Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD. Neurology 27 14557580
2022 Extracellular vesicles DJ-1 derived from hypoxia-conditioned hMSCs alleviate cardiac hypertrophy by suppressing mitochondria dysfunction and preventing ATRAP degradation. Pharmacological research 26 36509316
2020 The C terminus of DJ-1 determines its homodimerization, MGO detoxification activity and suppression of ferroptosis. Acta pharmacologica Sinica 25 33024240
2017 Expression of DJ-1 in Cancer Cells: Its Correlation with Clinical Significance. Advances in experimental medicine and biology 25 29147902
2010 α-Synuclein and DJ-1 as potential biological fluid biomarkers for Parkinson's Disease. International journal of molecular sciences 25 21151436
2005 Localization of DJ-1 protein in the murine brain. Cell and tissue research 25 16047164
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
2012 DJ-1 deficiency perturbs microtubule dynamics and impairs striatal neurite outgrowth. Neurobiology of aging 24 22609282
2016 DJ-1 deficiency attenuates expansion of liver progenitor cells through modulating the inflammatory and fibrogenic niches. Cell death & disease 23 27277679
2022 PARK7/DJ-1 as a Therapeutic Target in Gut-Brain Axis Diseases. International journal of molecular sciences 22 35743072
2011 The role of DJ-1 in the pathogenesis of endometriosis. PloS one 22 21445310
2011 DJ-1 mediates paraquat-induced dopaminergic neuronal cell death. Toxicology letters 21 21300143
2021 Extracellular DJ-1 induces sterile inflammation in the ischemic brain. PLoS biology 20 34014921