SPARQL | HTML5 RDFa and Microdata document
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http://www.w3.org/1999/02/22-rdf-syntax-ns#type
http://vocabularies.wikipathways.org/wp#Pathway
http://www.w3.org/2004/02/skos/core#Collection
http://vocabularies.wikipathways.org/wp#isAbout
http://rdf.wikipathways.org/Pathway/WP4357_r140180
http://vocabularies.wikipathways.org/wp#ontologyTag
http://vocabularies.wikipathways.org/wp#Curation:ONTOX
http://vocabularies.wikipathways.org/wp#Curation:AnalysisCollection
http://purl.obolibrary.org/obo/PW_0000378
http://vocabularies.wikipathways.org/wp#Curation:CPTAC
http://purl.obolibrary.org/obo/PW_0000369
http://vocabularies.wikipathways.org/wp#organism
http://purl.obolibrary.org/obo/NCBITaxon_9606
http://vocabularies.wikipathways.org/wp#organismName http://vocabularies.wikipathways.org/wp#pathwayOntologyTag
http://purl.obolibrary.org/obo/PW_0000369
http://purl.obolibrary.org/obo/PW_0000378
http://xmlns.com/foaf/0.1/img
https://www.wikipathways.org//wpi/wpi.php?action=downloadFile&type=svg&pwTitle=Pathway:WP4357&oldid=140180
https://www.wikipathways.org//wpi/wpi.php?action=downloadFile&type=png&pwTitle=Pathway:WP4357&oldid=140180
http://xmlns.com/foaf/0.1/page
http://www.wikipathways.org/instance/WP4357_r140180
http://purl.org/dc/elements/1.1/identifier
https://identifiers.org/wikipathways/WP4357
http://purl.org/dc/elements/1.1/source http://purl.org/dc/elements/1.1/title http://purl.org/dc/terms/description
Under basal conditions, Nrf2 is sequestered to the cytoplasm through binding with Keap1/Cul3/RBX1 and continually degraded via the proteasome. On early response to external stressors, Keap1 is oxidized or Nrf2 is phosphorylated by PKC. Nrf2 then translocates into the nucleus and binds to ARE (antioxidant-responsive) genes in order to increase or decrease transcription. A delayed response to external stressors causes phosphorylation of GSK-3β (by unknown tyrosine kinases), GSK-3β then activates Src kinases, which then translocate to the nucleus. Src kinases phosphorylate Nrf2 (Tyr568) which allows for nuclear export, ubiquitination and degradation of Nrf2. If insulin receptor signaling is initiated, GSK-3β activity is inhibited. Keap1 is also able to regulate Nrf2 activity through sequestration with PGAM5 to the mitochondria. In addition, PI3K also phosphorylates the CEBPB, inducing its translocation to the nucleus where it binds to the CEBPB response element within the xenobiotic response element, in conjunction with NRF2 binding to ARE.
Description was adapted from Fig 1 in Vomhof-Dekrey et al, and Fig 4 in Surh et al.
Protein phosphorylation sites were added based on information from [PhosphoSitePlus (R)](https://www.phosphosite.org).
http://purl.org/dc/terms/identifier http://purl.org/dc/terms/references
https://identifiers.org/pubmed/25514926
http://purl.org/spar/cito/cites
https://identifiers.org/pubmed/14570043
https://identifiers.org/pubmed/25514926
https://identifiers.org/pubmed/23434765
https://identifiers.org/pubmed/22819548