DJ1, also known asParkinson disease protein 7, is aprotein which in humans is encoded by thePARK7gene.[5] Its weak glyoxalase activity has been verified by many labs,[6] however the reported protein deglycase activity is likely to be an artifact stemming from DJ-1's ability to destroy free methylglyoxal.
The genePARK7, also known asDJ-1, encodes a protein of thepeptidase C56 family. The human genePARK7 has 8exons and locates at chromosome band 1p36.23.[5]
The human protein DJ-1 is 20kDa in size and composed of 189 amino acids with sevenβ-strands and nineα-helices in total and is present as adimer.[7][8][9] It belongs to thepeptidase C56 family of proteins.
The protein structures of human protein DJ-1,Escherichia colichaperone Hsp31, YhbO, and YajL and anArchaea protease are evolutionarily conserved.[10]
Under an oxidative condition, DJ-1 inhibits the aggregation ofα-synuclein via its chaperone activity,[11][12] thus functioning as a redox-sensitive chaperone and as a sensor foroxidative stress. Accordingly, DJ-1 apparently protects neurons against oxidative stress and cell death.[5] In parallel, protein DJ-1 acts as a positive regulator ofandrogen receptor-dependent transcription. DJ-1 is expressed in both the neural retina andretinal pigment epithelium of mammals, where it exerts a neuroprotective role against oxidative stress under both physiological and pathological conditions.[13][14]
Functional DJ-1 protein has been shown to bind metals and protect against metal-induced cytotoxicity fromcopper andmercury.[16]
DJ-1/PARK7 and its bacterial homologs: Hsp31, YhbO, and YajL can repairmethylglyoxal andglyoxalglycatednucleotides.[17]Guanine, either in the form of a free nucleotide or as a nucleotide incorporated intonucleic acid (DNA orRNA), if glycated, can be repaired by DJ-1/PARK7.[17] Deglycase-deficient bacterial mutants with reduced ability to repair glycated bases in DNA show strongmutator phenotypes.[17]
DJ-1 is aDNA damage response protein that is recruited to sites of DNA damage where it participates in therepair of DNA double-strand breaks through the processes ofnon-homologous end joining andhomologous recombination.[18] Evidence for a linkage between DNA damage andParkinson's disease has been reported for decades.[18] Recently evidence has been presented that defective DNA repair is linked specifically to DJ-1 mutation, and thus DJ-1 mutation likely contributes to Parkinson's disease pathogenesis.[18]
^Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL (Mar 2006). "The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein".Journal of Molecular Biology.356 (4):1036–48.doi:10.1016/j.jmb.2005.12.030.PMID16403519.
^Nunome K, Miyazaki S, Nakano M, Iguchi-Ariga S, Ariga H (Jul 2008). "Pyrroloquinoline quinone prevents oxidative stress-induced neuronal death probably through changes in oxidative status of DJ-1".Biological & Pharmaceutical Bulletin.31 (7):1321–6.doi:10.1248/bpb.31.1321.hdl:2115/53726.PMID18591768.
^Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (Jan 2003). "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism".Science.299 (5604):256–9.Bibcode:2003Sci...299..256B.doi:10.1126/science.1077209.PMID12446870.S2CID27186691.
^Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H (Feb 2003). "DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex".Molecular Cancer Research.1 (4):247–61.PMID12612053.
Bonifati V, Oostra BA, Heutink P (Mar 2004). "Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease".Journal of Molecular Medicine.82 (3):163–74.doi:10.1007/s00109-003-0512-1.PMID14712351.S2CID32685319.
Le W, Appel SH (Feb 2004). "Mutant genes responsible for Parkinson's disease".Current Opinion in Pharmacology.4 (1):79–84.doi:10.1016/j.coph.2003.09.005.PMID15018843.
Heutink P (2006). "PINK-1 and DJ-1 — new genes for autosomal recessive Parkinson's disease".Parkinson's Disease and Related Disorders. Journal of Neural Transmission. Supplementa. Vol. 70. pp. 215–9.doi:10.1007/978-3-211-45295-0_33.ISBN978-3-211-28927-3.PMID17017532.
Lev N, Roncevic D, Roncevich D, Ickowicz D, Melamed E, Offen D (2007). "Role of DJ-1 in Parkinson's disease".Journal of Molecular Neuroscience.29 (3):215–25.doi:10.1385/JMN:29:3:215.PMID17085780.S2CID85481215.
Nagakubo D, Taira T, Kitaura H, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (Feb 1997). "DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras".Biochemical and Biophysical Research Communications.231 (2):509–13.doi:10.1006/bbrc.1997.6132.PMID9070310.
Taira T, Takahashi K, Kitagawa R, Iguchi-Ariga SM, Ariga H (Jan 2001). "Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter".Gene.263 (1–2):285–92.doi:10.1016/S0378-1119(00)00590-4.PMID11223268.
Bonifati V, Dekker MC, Vanacore N, Fabbrini G, Squitieri F, Marconi R, Antonini A, Brustenghi P, Dalla Libera A, De Mari M, Stocchi F, Montagna P, Gallai V, Rizzu P, van Swieten JC, Oostra B, van Duijn CM, Meco G, Heutink P (Sep 2002). "Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7".Neurological Sciences.23 (Suppl 2): S59-60.doi:10.1007/s100720200069.PMID12548343.S2CID13625056.
Dekker M, Bonifati V, van Swieten J, Leenders N, Galjaard RJ, Snijders P, Horstink M, Heutink P, Oostra B, van Duijn C (Jul 2003). "Clinical features and neuroimaging of PARK7-linked parkinsonism".Movement Disorders.18 (7):751–7.doi:10.1002/mds.10422.PMID12815653.S2CID44253517.
