| http://purl.uniprot.org/citations/23555279 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23555279 | http://www.w3.org/2000/01/rdf-schema#comment | "The Nrf family of transcription factors plays a critical role in mediating adaptive responses to cellular stress and defends against neurodegeneration, aging, and cancer. Here, we report a novel role for the Caenorhabditis elegans Nrf homolog SKN-1 in regulating synaptic transmission at neuromuscular junctions (NMJs). Activation of SKN-1, either by acute pharmacological treatment with the mitochondrial toxin sodium arsenite or by mutations that cause constitutive SKN-1 activation, results in defects in neuromuscular function. Additionally, elimination of the conserved WD40 repeat protein WDR-23, a principal negative regulator of SKN-1, results in impaired locomotion and synaptic vesicle and neuropeptide release from cholinergic motor axons. Mutations that abolish skn-1 activity restore normal neuromuscular function to wdr-23 mutants and animals treated with toxin. We show that negative regulation of SKN-1 by WDR-23 in the intestine, but not at neuromuscular junctions, is necessary and sufficient for proper neuromuscular function. WDR-23 isoforms differentially localize to the outer membranes of mitochondria and to nuclei, and the effects of WDR-23 on neuromuscular function are dependent on its interaction with cullin E3 ubiquitin ligase. Finally, whole-transcriptome RNA sequencing of wdr-23 mutants reveals an increase in the expression of known SKN-1/Nrf2-regulated stress-response genes, as well as neurotransmission genes not previously implicated in SKN-1/Nrf2 responses. Together, our results indicate that SKN-1/Nrf2 activation may be a mechanism through which cellular stress, detected in one tissue, affects cellular function of a distal tissue through endocrine signaling. These results provide insight into how SKN-1/Nrf2 might protect the nervous system from damage in response to oxidative stress."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pgen.1003354"xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Sieburth D."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Knowles J.A."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Evgrafov O."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Corcoran C."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Staab T.A."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/author | "Griffen T.C."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/name | "PLoS Genet"xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/pages | "e1003354"xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/title | "The conserved SKN-1/Nrf2 stress response pathway regulates synaptic function in Caenorhabditis elegans."xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/23555279 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23555279 |
| http://purl.uniprot.org/citations/23555279 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23555279 |
| http://purl.uniprot.org/uniprot/P90794#attribution-6F1788B31027B42DD6E0B17D41776959 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/23555279 |
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| http://purl.uniprot.org/uniprot/P34707 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23555279 |
| http://purl.uniprot.org/uniprot/P90794 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23555279 |