Boyce, MichaelBryant, Kevin FJousse, CélineLong, KaiHarding, Heather PScheuner, DonalynKaufman, Randal JMa, DaweiCoen, Donald MRon, DavidYuan, Junying2020-01-012020-01-012005-020036-80751095-9203https://hdl.handle.net/10161/19707Most 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.Cell LinePC12 CellsEndoplasmic ReticulumAnimalsMiceRatsHerpesvirus 1, HumanKeratitis, HerpeticCinnamatesThioureaOxazolesProtein KinasesProteinsCell Cycle ProteinsEukaryotic Initiation Factor-2Viral ProteinsTunicamycinAntigens, DifferentiationEnzyme InhibitorsVirus ReplicationApoptosisProtein FoldingPhosphorylationCytoprotectionDose-Response Relationship, DrugGenes, ReporterMalePhosphoprotein PhosphatasesProtein Phosphatase 1Journal article2020-01-01