In vivo imaging of the spatiotemporal activity of the eIF2 -ATF4 signaling pathway: Insights into stress and related disorders - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Science Signaling Année : 2015

In vivo imaging of the spatiotemporal activity of the eIF2 -ATF4 signaling pathway: Insights into stress and related disorders

Résumé

The eIF2 alpha-ATF4 pathway is involved in cellular adaptation to stress and is dysregulated in numerous diseases. Activation of this pathway leads to phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha) and the recruitment of the transcription factor ATF4 (activating transcription factor 4) to specific CCAAT/enhancer binding protein (C/EBP)-ATF response elements (CAREs) located in the promoters of target genes. To monitor the spatiotemporal modulation of this pathway in living animals, we generated a novel CARE-driven luciferase mouse model (CARE-LUC). These transgenic mice enable the investigation of the eIF2 alpha-ATF4 pathway activity in the whole organism and at the tissue and cellular levels by combining imaging, luciferase assays, and immunochemistry. Using this mouse line, we showed the tissue-specific activation pattern of this pathway in response to amino acid deficiency or endoplasmic reticulum stress and the hepatic induction of this pathway in a stress-related pathology model of liver fibrosis. The CARE-LUC mouse model represents an innovative tool to investigate the eIF2 alpha-ATF4 axis and to develop drugs targeting this important pathway in the remediation of related pathologies.
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Dates et versions

hal-02459218 , version 1 (29-01-2020)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

C. Chaveroux, V. Carraro, L. Canaple, Julien Averous, Anne-Catherine Maurin, et al.. In vivo imaging of the spatiotemporal activity of the eIF2 -ATF4 signaling pathway: Insights into stress and related disorders. Science Signaling, 2015, 8 (374), pp.rs5-rs5. ⟨10.1126/scisignal.aaa0549⟩. ⟨hal-02459218⟩
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