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- Title
A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death.
- Authors
Boyce, M.; Py, B. F.; Ryazanov, A. G.; Minden, J. S.; Long, K.; Ma, D.; Yuan, J.
- Abstract
Apoptosis triggered by endoplasmic reticulum (ER) stress has been implicated in many diseases but its cellular regulation remains poorly understood. Previously, we identified salubrinal (sal), a small molecule that protects cells from ER stress-induced apoptosis by selectively activating a subset of endogenous ER stress-signaling events. Here, we use sal as a probe in a proteomic approach to discover new information about the endogenous cellular response to ER stress. We show that sal induces phosphorylation of the translation elongation factor eukaryotic translation elongation factor 2 (eEF-2), an event that depends on eEF-2 kinase (eEF-2K). ER stress itself also induces eEF-2K-dependent eEF-2 phosphorylation, and this pathway promotes translational arrest and cell death in this context, identifying eEF-2K as a hitherto unknown regulator of ER stress-induced apoptosis. Finally, we use both sal and ER stress models to show that eEF-2 phosphorylation can be activated by at least two signaling mechanisms. Our work identifies eEF-2K as a new component of the ER stress response and underlines the utility of novel small molecules in discovering new cell biology.Cell Death and Differentiation (2008) 15, 589–599; doi:10.1038/sj.cdd.4402296; published online 11 January 2008
- Subjects
CELL death; EUKARYOTIC cells; ENDOPLASMIC reticulum; APOPTOSIS; DEATH (Biology); CELLS
- Publication
Cell Death & Differentiation, 2008, Vol 15, Issue 3, p589
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4402296