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 | |
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] |