A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.
| dc.contributor.author | Boyce, Michael | |
| dc.contributor.author | Bryant, Kevin F | |
| dc.contributor.author | Jousse, Céline | |
| dc.contributor.author | Long, Kai | |
| dc.contributor.author | Harding, Heather P | |
| dc.contributor.author | Scheuner, Donalyn | |
| dc.contributor.author | Kaufman, Randal J | |
| dc.contributor.author | Ma, Dawei | |
| dc.contributor.author | Coen, Donald M | |
| dc.contributor.author | Ron, David | |
| dc.contributor.author | Yuan, Junying | |
| dc.date.accessioned | 2020-01-01T17:15:34Z | |
| dc.date.available | 2020-01-01T17:15:34Z | |
| dc.date.issued | 2005-02 | |
| dc.date.updated | 2020-01-01T17:15:34Z | |
| dc.description.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 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. | |
| dc.identifier | 307/5711/935 | |
| dc.identifier.issn | 0036-8075 | |
| dc.identifier.issn | 1095-9203 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | American Association for the Advancement of Science (AAAS) | |
| dc.relation.ispartof | Science (New York, N.Y.) | |
| dc.relation.isversionof | 10.1126/science.1101902 | |
| dc.subject | Cell Line | |
| dc.subject | PC12 Cells | |
| dc.subject | Endoplasmic Reticulum | |
| dc.subject | Animals | |
| dc.subject | Mice | |
| dc.subject | Rats | |
| dc.subject | Herpesvirus 1, Human | |
| dc.subject | Keratitis, Herpetic | |
| dc.subject | Cinnamates | |
| dc.subject | Thiourea | |
| dc.subject | Oxazoles | |
| dc.subject | Protein Kinases | |
| dc.subject | Proteins | |
| dc.subject | Cell Cycle Proteins | |
| dc.subject | Eukaryotic Initiation Factor-2 | |
| dc.subject | Viral Proteins | |
| dc.subject | Tunicamycin | |
| dc.subject | Antigens, Differentiation | |
| dc.subject | Enzyme Inhibitors | |
| dc.subject | Virus Replication | |
| dc.subject | Apoptosis | |
| dc.subject | Protein Folding | |
| dc.subject | Phosphorylation | |
| dc.subject | Cytoprotection | |
| dc.subject | Dose-Response Relationship, Drug | |
| dc.subject | Genes, Reporter | |
| dc.subject | Male | |
| dc.subject | Phosphoprotein Phosphatases | |
| dc.subject | Protein Phosphatase 1 | |
| dc.title | A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Boyce, Michael|0000-0002-2729-4876 | |
| pubs.begin-page | 935 | |
| pubs.end-page | 939 | |
| pubs.issue | 5711 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Biochemistry | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.publication-status | Published | |
| pubs.volume | 307 |
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