Specific cleavage of DJ-1 under an oxidative condition.
DJ-1 was initially identified by us as a novel oncogene and has recently been found to be a causative gene for familial Parkinson's disease (PD) PARK7. DJ-1 plays roles in transcriptional regulation and in oxidative stress function, and its oxidative state at cysteine residues determines activities of DJ-1. In this study, we found that recombinant DJ-1 expressed in and purified from E. coli was specifically cleaved between glycine and proline at amino acid numbers 157 and 158, respectively, by treatment of DJ-1 with H2O2. A substitution mutant of DJ-1 from cysteine to serine at amino acid number 106, a major oxidation site of DJ-1, was found not to be cleaved under an oxidative condition, suggesting oxidation-dependent cleavage of DJ-1. Cleavage of DJ-1 was also observed in human SH-SY5Y cells that had been treated with H2O2. These results suggest that oxidative stress-induced cleavage of DJ-1 regulates functions of DJ-1.
Ooe
Hiromasa
H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Maita
Chinatsu
C
Maita
Hiroshi
H
Iguchi-Ariga
Sanae M M
SM
Ariga
Hiroyoshi
H
D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D009447:Neuroblastoma; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011392:Proline / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D012694:Serine / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D016877:Oxidants; D012694:Serine; D011392:Proline; D006861:Hydrogen Peroxide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D003545:Cysteine; D005998:Glycine