DJ-1 Is a Copper Chaperone Acting on SOD1 Activation

Girotto, Stefania; Cendron, Laura; Bisaglia, Marco; Tessari, Isabella; Mammi, Stefano; Zanotti, Giuseppe; Bubacco, Luigi

doi:10.1074/jbc.m113.535112

Cited by 80 publications

(77 citation statements)

References 55 publications

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“…A noncovalent interaction of Prdx and DJ-1 may result from being similar-sized proteins, each from higher order oligomers. Indeed both Prdx and DJ-1 show overlap in function, each having both peroxidase (16,25) and molecular chaperone activities (9,22). The Cys-53 DJ-1-mediated interaction with Prdx2 is especially notable as most of the studies focus on Cys-106-mediated disulfide interactions with target proteins.…”

Section: Discussionmentioning

confidence: 99%

“…DJ-1 was first identified as an oncogene (2) and has since been described as a causative gene for early-onset Parkinson disease (3,4). Although DJ-1 has protease (5-7) or chaperone (8,9) activities, most studies have focused on its protective role against oxidative stress (10 -15). Knock-out of the DJ-1 gene enhances hydrogen peroxide (H 2 O 2 ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated cell death.…”

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confidence: 99%

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Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

Fernandez-Caggiano

Schröder

Cho

et al. 2016

Journal of Biological Chemistry

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The role and responses of the dimeric DJ-1 protein to cardiac oxidative stress is incompletely understood. H 2 O 2 induces a 50-kDa DJ-1 interprotein homodimer disulfide, known to form between Cys-53 on each subunit. A trimeric 75-kDa DJ-1 complex that mass spectrometry shows contained 2-Cys peroxiredoxin also formed and precedes the appearance of the disulfide dimer. These observations may represent peroxiredoxin sensing and transducing the oxidant signal to DJ-1. The dimeric disulfide DJ-1 complex was stabilized by auranofin, suggesting that thioredoxin recycles it in cells. Higher concentrations of H 2 O 2 concomitantly induce DJ-1 Cys-106 hyperoxidation (sulfination or sulfonation) in myocytes, perfused heart, or HEK cells. An oxidation-resistant C53A DJ-1 shows potentiated H 2 O 2 -induced Cys-106 hyperoxidation. DJ-1 also forms multiple disulfides with unknown target proteins during H 2 O 2 treatment, the formation of which is also potentiated in cells expressing the C53A mutant. This suggests that the intersubunit disulfide induces a conformational change that limits Cys-106 forming heterodisulfide protein complexes or from hyperoxidizing. High concentrations of H 2 O 2 also induce cell death, with DJ-1 Cys-106 sulfonation appearing causal in these events, as expression of C53A DJ-1 enhanced both Cys-106 sulfonation and cell death. Nonetheless, expression of the DJ-1 C106A mutant, which fully prevents hyperoxidation, also showed exacerbated cell death responses to H 2 O 2 . A rational explanation for these findings is that DJ-1 Cys-106 forms disulfides with target proteins to limit oxidantinduced cell death. However, when Cys-106 is hyperoxidized, formation of these potentially protective heterodimeric disulfide complexes is limited, and so cell death is exacerbated.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

Fernandez-Caggiano

Schröder

Cho

et al. 2016

Journal of Biological Chemistry

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“…11 Both structures are virtually identical to each other [root-mean-square deviation (rmsd) of 0.15 Å] (Figure 2 and Figure S3 of the Supporting Information) and to other structures of DJ-1 (rmsd of ≤0.15 Å). 4,5,11 The electron density maps of our two crystal structures reveal a large peak in the immediate vicinity of the key residue Cys106 of DJ-1. This peak is not observed in crystals of apo-DJ-1, 11,12 suggesting the presence of Zn(II) at this position ( Figure 2b and Figure S3 of the Supporting Information).…”

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confidence: 96%

Thermodynamic and Structural Characterization of the Specific Binding of Zn(II) to Human Protein DJ-1

Tashiro

Caaveiro

et al. 2014

Biochemistry

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Mutations of DJ-1 cause familial Parkinson's disease (PD), although the role of DJ-1 in PD remains unresolved. Very recent reports have shown that DJ-1 interacts with copper ions. This evidence opens new avenues to understanding the function of DJ-1 and its role in PD. Herein, we report that Zn(II) binds to DJ-1 with great selectivity among the other metals examined: Mn(II), Fe(II), Co(II), Ni(II), and Cu(II). High-resolution X-ray crystallography (1.18 Å resolution) shows Zn(II) is coordinated to the protein by the key residues Cys106 and Glu18. These results suggest that DJ-1 may be regulated and/or stabilized by Zn(II).

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“…166,167) Furthermore, DJ-1 directly binds to SOD1 to regulate its activity. [168][169][170] Although DJ-1 is an abundant protein in cells, the contribution level of reduction of oxidative stress by quenching ROS through self-oxidation of DJ-1 is thought to be less than 10% of the total contribution, and aforementioned reactions 2) and 3) contribute to the rest of the anti-oxidative stress function. DJ-1 mutants observed in PD patients have loss of or weaken anti-oxidative stress activity, 171) and DJ-1-knockout mice are more vulnerable to neuronal toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydr (MPTP) than are wild-type mice.…”

Section: Anti-oxidative Stress Functionmentioning

confidence: 99%

Common Mechanisms of Onset of Cancer and Neurodegenerative Diseases

Ariga

2015

Biological & Pharmaceutical Bulletin

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Onset of cancer and neurodegenerative disease occurs by abnormal cell growth and neuronal cell death, respectively, and the number of patients with both diseases has been increasing in parallel with an increase in mean lifetime, especially in developed countries. Although both diseases are sporadic, about 10% of the diseases are genetically inherited, and analyses of such familial forms of gene products have contributed to an understanding of the molecular mechanisms underlying the onset and pathogenesis of these diseases. I have been working on c-myc, a protooncogene, for a long time and identified various c-Myc-binding proteins that play roles in c-Myc-derived tumorigenesis. Among these proteins, some proteins have been found to be also responsible for the onset of neurodegenerative diseases, including Parkinson's disease, retinitis pigmentosa and cerebellar atrophy. In this review, I summarize our findings indicating the common mechanisms of onset between cancer and neurodegenerative diseases, with a focus on genes such as DJ-1 and Myc-Modulator 1 (MM-1) and signaling pathways that contribute to the onset and pathogenesis of cancer and neurodegenerative diseases.

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DJ-1 Is a Copper Chaperone Acting on SOD1 Activation

Cited by 80 publications

References 55 publications

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2

Thermodynamic and Structural Characterization of the Specific Binding of Zn(II) to Human Protein DJ-1

Common Mechanisms of Onset of Cancer and Neurodegenerative Diseases

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