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Science 332 (6025): 44-45

Copyright © 2011 by the American Association for the Advancement of Science

Phosphatase Inhibition Delays Translational Recovery

R. Luke Wiseman1, and Jeffery W. Kelly1,2,3

1 Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
2 Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
3 Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA.


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Enhancing proteostasis. Guanabenz selectively inhibits the GADD34-mediated negative feedback loop of PERK signaling through direct binding to GADD34, preventing its association with protein phosphatase 1 (PP1). As a result, guanabenz extends translational attenuation in response to ER stress, increasing chaperone-to-substrate ratios and alleviating protein misfolding within the ER lumen.

 


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