| http://purl.uniprot.org/citations/21245377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21245377 | http://www.w3.org/2000/01/rdf-schema#comment | "Regulation of transcription factor Nrf2 (NF-E2-related factor 2) involves redox-sensitive proteasomal degradation via the E3 ubiquitin ligase Keap1/Cul3. However, Nrf2 is controlled by other mechanisms that have not yet been elucidated. We now show that glycogen synthase kinase 3 (GSK-3) phosphorylates a group of Ser residues in the Neh6 domain of mouse Nrf2 that overlap with an SCF/β-TrCP destruction motif (DSGIS, residues 334 to 338) and promotes its degradation in a Keap1-independent manner. Nrf2 was stabilized by GSK-3 inhibitors in Keap1-null mouse embryo fibroblasts. Similarly, an Nrf2(ΔETGE) mutant, which cannot be degraded via Keap1, accumulated when GSK-3 activity was blocked. Phosphorylation of a Ser cluster in the Neh6 domain of Nrf2 stimulated its degradation because a mutant Nrf2(ΔETGE 6S/6A) protein, lacking these Ser residues, exhibited a longer half-life than Nrf2(ΔETGE). Moreover, Nrf2(ΔETGE 6S/6A) was insensitive to β-TrCP regulation and exhibited lower levels of ubiquitination than Nrf2(ΔETGE). GSK-3β enhanced ubiquitination of Nrf2(ΔETGE) but not that of Nrf2(ΔETGE 6S/6A). The Nrf2(ΔETGE) protein but not Nrf2(ΔETGE 6S/6A) coimmunoprecipitated with β-TrCP, and this association was enhanced by GSK-3β. Our results show for the first time that Nrf2 is targeted by GSK-3 for SCF/β-TrCP-dependent degradation. We propose a "dual degradation" model to describe the regulation of Nrf2 under different pathophysiological conditions."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.01204-10"xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "Hayes J.D."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "McMahon M."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "Cuadrado A."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "Chowdhry S."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "Rada P."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/author | "Rojo A.I."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/pages | "1121-1133"xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/title | "SCF/{beta}-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner."xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://purl.uniprot.org/core/volume | "31"xsd:string |
| http://purl.uniprot.org/citations/21245377 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21245377 |
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