Cysteine Sulfenylation Directs IRE-1 to Activate the SKN-1/Nrf2 Antioxidant Response.
Mol Cell
; 63(4): 553-566, 2016 08 18.
Article
em En
| MEDLINE
| ID: mdl-27540856
Emerging evidence suggests that many proteins may be regulated through cysteine modification, but the extent and functions of this signaling remain largely unclear. The endoplasmic reticulum (ER) transmembrane protein IRE-1 maintains ER homeostasis by initiating the unfolded protein response (UPR(ER)). Here we show in C. elegans and human cells that IRE-1 has a distinct redox-regulated function in cytoplasmic homeostasis. Reactive oxygen species (ROS) that are generated at the ER or by mitochondria sulfenylate a cysteine within the IRE-1 kinase activation loop. This inhibits the IRE-1-mediated UPR(ER) and initiates the p38/SKN-1(Nrf2) antioxidant response, thereby increasing stress resistance and lifespan. Many AGC-family kinases (AKT, p70S6K, PKC, ROCK1) seem to be regulated similarly. The data reveal that IRE-1 has an ancient function as a cytoplasmic sentinel that activates p38 and SKN-1(Nrf2) and indicate that cysteine modifications induced by ROS signals can direct proteins to adopt unexpected functions and may coordinate many cellular processes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Serina-Treonina Quinases
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Caenorhabditis elegans
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Cisteína
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Proteínas de Caenorhabditis elegans
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Proteínas de Ligação a DNA
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Endorribonucleases
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Fator 2 Relacionado a NF-E2
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Antioxidantes
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article