| http://purl.uniprot.org/citations/22492997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22492997 | http://www.w3.org/2000/01/rdf-schema#comment | "DJ-1, which is linked to recessively inherited Parkinson's disease when mutated, is a multi-functional protein with anti-oxidant and transcription regulatory activities. However, the mechanism(s) through which DJ-1 and the genes it regulates provide neuroprotection is not fully understood. Here, we show that wild-type DJ-1 induces the expression of thioredoxin 1 (Trx1), a protein disulfide oxidoreductase, whereas pathogenic mutant isoforms L166P and M26I cannot. Conversely, DJ-1 knockdown in SH-SY5Y cells and DJ-1 knockout in mice result in significant decrease in Trx1 protein and mRNA expression levels. The importance of Trx1 in the cytoprotective function of DJ-1 is confirmed using a pharmacological inhibitor of Trx reductase, 1-chloro-2,4-dinitrobenzene, and Trx1 siRNA. Both approaches result in partial loss of DJ-1-mediated protection. Additionally, knockdown of Trx1 significantly abrogates DJ-1-dependent, hydrogen peroxide-induced activation of the pro-survival factor AKT. Promoter analysis of the human Trx1 gene identified an antioxidant response element (ARE) that is required for DJ-1-dependent induction of Trx1 expression. The transcription factor Nuclear factor erythroid-2 related factor 2 (Nrf2), which is a critical inducer of ARE-mediated expression, is regulated by DJ-1. Overexpression of DJ-1 results in increased Nrf2 protein levels, promotes its translocation into the nucleus and enhances its recruitment onto the ARE site in the Trx1 promoter. Further, Nrf2 knockdown abolishes DJ-1-mediated Trx1 induction and cytoprotection against hydrogen peroxide, indicating the critical role of Nrf2 in carrying out the protective functions of DJ-1 against oxidative stress. These findings provide a new mechanism to support the antioxidant function of DJ-1 by increasing Trx1 expression via Nrf2-mediated transcriptional induction."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/dds131"xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/author | "Lee K.W."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/author | "Mouradian M.M."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/author | "Im J.Y."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/author | "Junn E."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/author | "Woo J.M."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/name | "Hum Mol Genet"xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/pages | "3013-3024"xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/title | "DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway."xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://purl.uniprot.org/core/volume | "21"xsd:string |
| http://purl.uniprot.org/citations/22492997 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22492997 |
| http://purl.uniprot.org/citations/22492997 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22492997 |
| http://purl.uniprot.org/uniprot/Q16236#attribution-8F24801C22AB2F363DC44BC2084380B9 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22492997 |
| http://purl.uniprot.org/uniprot/Q99497#attribution-8F24801C22AB2F363DC44BC2084380B9 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22492997 |
| http://purl.uniprot.org/uniprot/Q99497#attribution-FE981BB8C25B285B0DB83A4137D7BBBF | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22492997 |
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| http://purl.uniprot.org/uniprot/P10599#attribution-4600CFBB9C376A7FF6C094A915D767C3 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22492997 |
| http://purl.uniprot.org/uniprot/P10599#attribution-FE981BB8C25B285B0DB83A4137D7BBBF | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22492997 |
| http://purl.uniprot.org/uniprot/#_E2I973-mappedCitation-22492997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22492997 |
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| http://purl.uniprot.org/uniprot/#_A2A815-mappedCitation-22492997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22492997 |