A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Boyce, M; Bryant, KF; Jousse, C; Long, K; Harding, HP; Scheuner, D; Kaufman, RJ; Ma, D; Coen, DM; Ron, D; Yuan, J

Published Date

  • February 11, 2005

Published In

Volume / Issue

  • 307 / 5711

Start / End Page

  • 935 - 939

PubMed ID

  • 15705855

Pubmed Central ID

  • 15705855

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1101902

Language

  • eng

Conference Location

  • United States