PARK7

Official Full Name

Parkinsonism associated deglycase

Organism

Homo sapiens

GeneID

11315

Background

The product of this gene belongs to the peptidase C56 family of proteins. It acts as a positive regulator of androgen receptor-dependent transcription. It may also function as a redox-sensitive chaperone, as a sensor for oxidative stress, and it apparently protects neurons against oxidative stress and cell death. Defects in this gene are the cause of autosomal recessive early-onset Parkinson disease 7. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

Synonyms

DJ1; DJ-1; GATD2; HEL-S-67p;

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Detailed Information

PARK7 works as a potential anti-Parkinson's disease therapeutic target

The 189 amino acids comprised human PARK7 protein, also known as DJ-1, is a small ubiquitously expressed protein at 20 kDa with over-expression in various tissues, including the testes, sperm, and the brain. Early onset of autosomal recessive Parkinson's disease (PD) with various symptoms, including dyskinesia, rigidity, and tremors, can be incurred by the homozygous deletions and missense mutations in PARK7. The L166P, L10P, T19L, R26A, D149, G78G, M26I, R98Q, D149A, L172Q and L172G mutations, were identified to be involved in the pathogenesis of PD, within which they mainly reduce the stability of PARK7 to exert their influence, however, DJ-1 mutants, R98Q, D149A, and L166P mutations have involvement in the pathogenesis via inducing mitochondrial dysfunction. In addition to this, the expression of PARK7 can be reduced by L166P, L172Q, L10P mutations for its rapid degradation induction. The mutations of D149A are unlike to the L166P mutation in the p53-mediated cell death, the former one is resorted to stabilize the PARK7 via caspase-6 inhibited cleavage, the last one is reducing the expression level of PARK7 through rapid proteolysis.

Oxidation of the catalytic C106 residue mediated aggregation of PARK7 has also been found to be associated with the pathogenicity of PD, for the formation of amyloid-β plaques can give rise to alterations in the PARK7 folding. PARK7 is aggregated by the interactions between PARK7 and α-synuclein. Aggregation of PARK7 induced loss of function may be resulted from deletion mutations and missense mutations. Owing to the loss of the molecular chaperone function of PARK7 caused by the aggregation of PARK7, L166P and R28A mutation inhibited dimer formation cannot inhibit the formation of α-synuclein aggregates.

PARK7 works as an apoptosis suppressor in cancer cells

Apoptosis of cancer cells can be suppressed by PARK7 expression, like the H2O2 or mitomycin C (MMC) induced apoptosis is markedly reduced by the overexpression of PARK7, this protective effect can mainly resort to the inhibition of specific inducer of apoptosis, the tumor necrosis factor-related apoptosis-inducing ligand (TNFSF10). Survivin was up-regulated by PARK7 to inhibit apoptotic proteins, thus inducing the proliferation of laryngeal carcinoma cells. Autophagy can be inhibited by PARK7 via the suppression of JNK activity and the transcription of Beclin induced by increasing the formation of the PARK7/MEP3K1 complex.

Figure 1. PARK7 enhance the proliferation and aggressiveness of cancer cells by regulating the activity of several proteins via direct interactions. (Wook Jin, et al. 2020)

References:

Jin W. Novel insights into PARK7 (DJ-1), a potential anti-cancer therapeutic target, and implications for cancer progression. Journal of Clinical Medicine, 2020, 9(5): 1256.
Neumann M, Müller V, Görner K, et al. Pathological properties of the Parkinson's disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease. Acta neuropathologica, 2004, 107(6): 489-496.

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