Stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress.
J Cell Biol
; 219(7)2020 07 06.
Article
en En
| MEDLINE
| ID: mdl-32349127
ABSTRACT
Membrane integrity at the endoplasmic reticulum (ER) is tightly regulated, and its disturbance is implicated in metabolic diseases. Using an engineered sensor that activates the unfolded protein response (UPR) exclusively when normal ER membrane lipid composition is compromised, we identified pathways beyond lipid metabolism that are necessary to maintain ER integrity in yeast and in C. elegans. To systematically validate yeast mutants that disrupt ER membrane homeostasis, we identified a lipid bilayer stress (LBS) sensor in the UPR transducer protein Ire1, located at the interface of the amphipathic and transmembrane helices. Furthermore, transcriptome and chromatin immunoprecipitation analyses pinpoint the UPR as a broad-spectrum compensatory response wherein LBS and proteotoxic stress deploy divergent transcriptional UPR programs. Together, these findings reveal the UPR program as the sum of two independent stress responses, an insight that could be exploited for future therapeutic intervention.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
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Glicoproteínas de Membrana
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Proteínas Serina-Treonina Quinasas
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Caenorhabditis elegans
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Proteínas de Saccharomyces cerevisiae
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Proteínas de Caenorhabditis elegans
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Respuesta de Proteína Desplegada
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Estrés del Retículo Endoplásmico
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Proteínas de Choque Térmico
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Membrana Dobles de Lípidos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Singapur