Research ResourceSTRESS SIGNALING

In vivo imaging of the spatiotemporal activity of the eIF2α-ATF4 signaling pathway: Insights into stress and related disorders

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Science Signaling  28 Apr 2015:
Vol. 8, Issue 374, pp. rs5
DOI: 10.1126/scisignal.aaa0549

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Seeing stress signaling in living mice

In response to cellular stress, activation of the eIF2α-ATF4 pathway reduces global protein production while enhancing targeted adaptive gene expression to enable cells to adapt and survive. Activation of this pathway is associated with various disease pathologies, such as tissue fibrosis after injury, oxidative stress, or chemically induced damage. Chaveroux et al. developed a transgenic mouse model in which the activation of this pathway could be monitored at the level of the whole animal by bioluminescence imaging and at the tissue and cellular levels by quantification and visualization of the enzyme activity. Analysis of these mice revealed that activation of this pathway is tissue-specific, depending on the initiating stress, and also showed that chemically induced liver fibrosis correlates with activation of the eIF2α-ATF4 pathway by a specific kinase.

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