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A Selective Inhibitor of eIF2α Dephosphorylation Protects Cells from ER Stress
Abstract
Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit α (eIF2α). Salubrinal also blocks eIF2α dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2α dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.
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Citations
Cited by
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Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
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Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. (2008) · Science · doi:10.1126/science.1141448 · Cited by 2,495
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Metadata
- Authors
- Boyce, M., Bryant, K. F., Jousse, C., Long, K., Harding, H. P., Scheuner, D., Kaufman, R. J., Ma, D., Coen, D. M., Ron, D., & Yuan, J.
- Venue
- Science
- Published
- 2005-02-11
- Volume
- 307
- Issue
- 5711
- Pages
- 935-939
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2140487984
- Cited by
- 1,403
- References
- 0
- FWCI
- 20.16
- Type
- journal article
- Language
- en
- Open access
- closed
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- Boyce, M., Bryant, K. F., Jousse, C., Long, K., Harding, H. P., Scheuner, D., Kaufman, R. J., Ma, D., Coen, D. M., Ron, D., & Yuan, J. (2005). A Selective Inhibitor of eIF2α Dephosphorylation Protects Cells from ER Stress. Science. https://doi.org/10.1126/science.1101902
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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