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Table 1 DJ-1 functions described to date

From: PARK7/DJ-1 in microglia: implications in Parkinson’s disease and relevance as a therapeutic target

Function

Model

References

Functions as an oncogene

 Suppresses phosphatase PTEN

Drosophila melanogaster, COS7 (monkey fibroblast cell line), NIH3T3 (mouse fibroblast cell line)

[177]

 Alters p53 signaling

HEK293T (human kidney cell line), A549 (human lung adenocarcinoma cell line), H1299 (human lung carcinoma cell line), DJ1 KO primary mouse fibroblast

[178]

N2a (mouse neuroblastoma cell line), HEK293T, A549, H1299, Danio rerio

[179]

HEK293T, H1299, HeLa (human cervical cancer cell line),

[180]

ME180 (mouse tumor associated endothelial cell line)

[181]

 Cooperative transforming activity with H-ras

NIH3T3, HeLa, Cos I (monkey fibroblast cell line), 3Y1 (rat fibroblast cell line)

[66]

Functions in antioxidant responses

 Upregulates glutathione (GSH) synthesis

  Via the inhibition of GSH inhibitor protein glutathione-specific gamma-glutamylcyclotransferase (CHAC1)

N27 (rat dopaminergic neuron cell line), primary rat mesencephalic cells

[97]

HEK293T, primary mouse astrocytes

[98]

 Stabilizes NRF2

  Via the upregulation of thioredoxin 1

Primary mouse embryonic fibroblasts, Huh7 (human liver cancer cell line), H157 (human oral squamous carcinoma cell line)

[90]

SH-SY5Y (human dopaminergic neuroblastoma cell line), HeLa

[118]

 Protects against oxidative stress to prevent cell death

  Via an interaction with Daxx to suppress cell death

  Via the binding to subunit of NADPH oxidase to prevent oxidative burst

  DJ-1 protects against cell death induced by oxidative, but not nonoxidative, stress following MPTP-treatment in vivo

  Stronger intracellular ROS response with and without LPS treatment in DJ-1 deficient microglia compared to wildtype

H1299, HEK293T

[96]

NIH3T3, SH-SY5Y

[92]

HeLa, SH-SY5Y

[182]

SH-SY5Y

[72]

Bone marrow-derived macrophages from mice and humans, THP-1 (human monocytic cell line), RAW 264.7 (mouse monocytic cell line)

[113]

[112]

MPTP-model of PD in DJ-1 KO mice

[110]

DJ-1 deficient N9 (immortalized murine microglia cell line)

[111]

Other functions of DJ-1

 Interacts with PINK1 and PARKIN

SH-SY5Y, HEK293

SH-SY5Y

[183, 184]

 Acts as a redox sensitive chaperone

SH-SY5Y, HEK293, Undifferentiated murine ES cells, HeLa, CAD (mouse neuroblastoma cell line)

[70]

 Prevents damage to proteins and metabolites caused by 1,3-biphosphoglycerate

HCT 116 (human colon cancer cell line), Drosophila melanogaster, Schizosaccharomyces pombe, Escherichia coli

[185]

 Autophagy and phagocytosis of α-syn and mitochondria

N9 (mouse microglia cell line), primary mouse microglia

[71]

DJ-1 KO mouse embryonic fibroblasts, DJ-1 KO mouse primary cortical neurons, DJ-1 KO mouse primary lymphoblasts, H1299

[192]

DJ-1 KO mouse embryonic fibroblasts, primary human fibroblast from DJ-1 mutated patients (E46D homozygous mutation)

[186]

 Mitochondrial homeostasis

DJ-1 KO mouse embryonic fibroblasts, DJ-1 KO mouse primary cortical neurons, DJ-1 KO mouse primary lymphoblasts, H1299

[187]

N9 (mouse microglia cell line), primary mouse microglia

[71]

SN4741 (mouse dopaminergic neuron cell line)

[188]

 Controls metabolic pathways

 Promote pyruvate dehydrogenase (PDH) activity by binding to PDHE1-β, a component of the PDH complex, inhibiting phosphorylation and thereby promoting oxidative phosphorylation

Drosophila melanogaster, DJ-1 deficient SH-SY5Y

[189]

Aged DJ-1 KO mice

[32]

 Acts as a protease

H1299, HEK293, HEK293T

[96]

DJ-1 crystallography (in silico prediction), (Flp-In)NIH3T3

[99]

D2 (mouse mammary gland tumor cell line), HEK293T

[190]

 Modulates androgen-receptor signaling

HEK293T, TM4 (mouse Sertoli cell line), HepG2 (human liver carcinoma cell line), Cos I, CV1 (monkey fibroblast cell line)

[191]

COS7

[192]

H1299, HEK293T, LNCaP (human prostate cancer cell line), LAPC4 (human prostate cancer cell line)

[193]

 Alters dopamine receptor signaling

Acute striatal slices from DJ-1 KO mice

[194]

HEK293T

[195]

SH-SY5Y, SK-N-SH (human neuroblastoma cell line)

[196]

 Inhibits aggregation of α-synuclein

SH-SY5Y, DJ-1 KO mice

[197]

HEK293T, H4 (Human neuroglioma cell line), undifferentiated murine ES cells, HeLa, SH-SY5Y

[198]

Undifferentiated murine ES cells, HeLa, CAD

[70]

 Binding of STAT1 phosphatase

Primary mouse DJ-1 KO microglia and astrocytes, DJ-1 KO mouse cortical slices, BV-2 (mouse microglia cell line)

[131]

 Binding of p65 (subunit of NFκB)

DJ-1 KO mouse, BV-2

[133]