Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

@inproceedings{Sidrauski2015PharmacologicalDA,
  title={Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response},
  author={Carmela Sidrauski and Jordan C Tsai and Martin Kampmann and Brian R. Hearn and Punitha Vedantham and Priyadarshini Jaishankar and Masaaki Sokabe and Aaron S. Mendez and Billy W. Newton and Edward L Tang and Erik Verschueren and Jeffrey R. Johnson and Nevan J. Krogan and Christopher S. Fraser and Jonathan S. Weissman and Adam R. Renslo and Peter J. Walter},
  booktitle={eLife},
  year={2015}
}
The general translation initiation factor eIF2 is a major translational control point. Multiple signaling pathways in the integrated stress response phosphorylate eIF2 serine-51, inhibiting nucleotide exchange by eIF2B. ISRIB, a potent drug-like small molecule, renders cells insensitive to eIF2α phosphorylation and enhances cognitive function in rodents by blocking long-term depression. ISRIB was identified in a phenotypic cell-based screen, and its mechanism of action remained unknown. We now… CONTINUE READING
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