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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

In cells, various signaling pathways help to maintain proteostasis—the proper concentrations, folding, and function of proteins. When a cell is under stress, upstream "stress sensors" within these pathways are activated, initiating a signaling cascade that minimizes the misfolding and aggregation of proteins, which can lead to disease (13). Stress sensors often respond to the accumulation of misfolded proteins within specific cell compartments by activating the transcription of proteostasis components, such as enzymes and "chaperone" proteins that assist with folding or by attenuating new protein synthesis. The propagation of stress-response signaling is often mediated by phosphorylation, or the addition of a phosphate group to the stress sensor and/or downstream signaling components. Because of the central importance of stress signaling pathways in maintaining the integrity of the cellular proteome, manipulating these pathways has become an attractive strategy for preventing the protein misfolding linked to numerous human diseases (4, 5).

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.

E-mail: wiseman{at}; jkelly{at}

Chemical and Biological Approaches for Adapting Proteostasis to Ameliorate Protein Misfolding and Aggregation Diseases-Progress and Prognosis.
S. L. Lindquist and J. W. Kelly (2011)
Cold Spring Harb Perspect Biol 3, a004507
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