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Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in the pathogenesis of many common human diseases. Integral to the UPR and an important determinant in cell fate is the expression of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This is promoted by activating transcription factor 4 (ATF4) whose expression is rapidly up-regulated in response to ER stress through an eIF2α phosphorylation-dependent increase in protein synthesis. Our data demonstrates that this ER stress-induced increase in ATF4 and CHOP expression is initiated by an increase in Atf4 and Chop mRNA, which is also dependent upon eIF2α phosphorylation. Despite being dependent on eIF2α phosphorylation, we provide evidence that these increases in Atf4 and Chop mRNA expression may occur independently of de novo protein synthesis. Moreover, we show that ER stress-induced Chop mRNA expression is exacerbated by Sirtuin-1 (SIRT1) inhibition indicating that changes in the energy status of the cell may play an important role in its regulation. This work highlights and extends previous findings, and provides important new insights into the mechanism of ER stress-induced expression of Atf4 and Chop mRNA that clearly warrants further investigation.

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Faculty of Technology ePrints Service  


Chan, S. M. H. -  Zhao, X. -  Elfowiris, A. -  Ratnam, C. -  Herbert, T. P. - 

Id.: 70120495

Idioma: inglés  - 

Versión: 1.0

Estado: Final

Tipo:  application/pdf - 

Palabras claveB200 Pharmacology, Toxicology and Pharmacy - 

Tipo de recurso: Article  -  PeerReviewed  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Formatos:  application/pdf - 

Requerimientos técnicos:  Browser: Any - 

Relación: [References] http://eprints.lincoln.ac.uk/28210/
[References] 10.1016/j.biochi.2017.04.018

Fecha de contribución: 08-nov-2017


* Chan, S. M. H. and Zhao, X. and Elfowiris, A. and Ratnam, C. and Herbert, T. P. (2017) The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells. Biochimie, 138 . pp. 156-167. ISSN 0300-9084

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