A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.
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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 alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha 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.
Herpesvirus 1, Human
Cell Cycle Proteins
Eukaryotic Initiation Factor-2
Dose-Response Relationship, Drug
Protein Phosphatase 1
Published Version (Please cite this version)10.1126/science.1101902
Publication InfoBoyce, Michael; Bryant, Kevin F; Jousse, Céline; Long, Kai; Harding, Heather P; Scheuner, Donalyn; ... Yuan, Junying (2005). A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science (New York, N.Y.), 307(5711). pp. 935-939. 10.1126/science.1101902. Retrieved from https://hdl.handle.net/10161/19707.
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Michael Scott Boyce
Associate Professor of Biochemistry
The Boyce Lab studies mammalian cell signaling through protein glycosylation. For the latest news, project information and publications from our group, please visit our web site at http://www.boycelab.org or follow us on Twitter at https://twitter.com/BoyceLab.
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