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http://purl.uniprot.org/citations/22683601http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22683601http://www.w3.org/2000/01/rdf-schema#comment"Loss-of-function mutations in the PARK7/DJ-1 gene cause early onset autosomal-recessive Parkinson disease. DJ-1 has been implicated in protection of neurons from oxidative stress and in regulation of transcriptional activity. However, whether there is a relationship between the subcellular localization of DJ-1 and its function remains unknown. Therefore, we examined the subcellular localization of DJ-1 during dopaminergic neurodegeneration induced by various insults. Immunoblotting and immunocytochemistry showed that the nuclear pool of DJ-1 dramatically increased in both MN9D dopaminergic neuronal cells and primary cultures of mesencephalic dopaminergic neurons after 6-hydroxydopamine (6-OHDA) treatment. This was paralleled by a corresponding decrease in its cytosolic level, indicating drug-induced nuclear translocation of DJ-1. The same phenomenon was detected in other cell death paradigms induced by pro-oxidants including hydrogen peroxide and cupric chloride. Consequently, cotreatment with the antioxidant N-acetyl-l-cysteine blocked the translocation of DJ-1 into the nucleus. However, mutation at cysteine 106 had no effect on the translocation of DJ-1 into the nucleus, suggesting that reactive oxygen species-mediated downstream signaling and/or modifications other than oxidative modification are involved in its nuclear translocation. Ectopic expression of nucleus localization signal (NLS)-tagged DJ-1 prevented cell death from 6-OHDA. We investigated whether nuclear DJ-1 was involved in transcriptional regulation and found that DJ-1 was localized in promyelocytic leukemia bodies, and this localization increased upon 6-OHDA treatment. We also confirmed that binding of DJ-1 and promyelocytic leukemia bodies indeed increased after 6-OHDA treatment. Consequently, expression levels of acetylated p53 and PUMA were downregulated in cells overexpressing DJ-1 or NLS-tagged DJ-1. Taken together, our data suggest that nuclear translocation of DJ-1 may protect neurons from cell death after oxidative stress."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.org/dc/terms/identifier"doi:10.1016/j.freeradbiomed.2012.05.035"xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Kim S.J."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Park Y.J."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Park K.S."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Oh Y.J."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Hwang I.Y."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/author"Youdim M.B."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/name"Free Radic Biol Med"xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/pages"936-950"xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/title"Nuclear translocation of DJ-1 during oxidative stress-induced neuronal cell death."xsd:string
http://purl.uniprot.org/citations/22683601http://purl.uniprot.org/core/volume"53"xsd:string
http://purl.uniprot.org/citations/22683601http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22683601
http://purl.uniprot.org/citations/22683601http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22683601
http://purl.uniprot.org/uniprot/Q99497#attribution-1F93AB7C3435D26A3BD5422E001C0880http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22683601