| First Author | Chaveroux C | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 374 | Pages | rs5 |
| PubMed ID | 25921292 | Mgi Jnum | J:260170 |
| Mgi Id | MGI:6142698 | Doi | 10.1126/scisignal.aaa0549 |
| Citation | Chaveroux C, et al. (2015) In vivo imaging of the spatiotemporal activity of the eIF2alpha-ATF4 signaling pathway: Insights into stress and related disorders. Sci Signal 8(374):rs5 |
| abstractText | The eIF2alpha-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 (eIF2alpha) 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 eIF2alpha-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 eIF2alpha-ATF4 axis and to develop drugs targeting this important pathway in the remediation of related pathologies. |
