Cell Biology Stress Relief

Stella M. Hurtley

Science, AAAS, Cambridge CB2 1LQ, UK

The reversible phosphorylation of proteins allows cells to adapt to sudden changes in their environment. Tsaytler et al. (see the Perspective by Wiseman and Kelly) describe a specific small-molecule inhibitor of a regulatory subunit of protein phosphatase 1, guanabenz. Guanabenz selectively bound to a regulatory subunit of protein phosphatase 1 and selectively disrupted the stress-induced dephosphorylation of a subunit of translation initiation factor 2, thereby prolonging translation attenuation in stressed cells. This favored protein folding, promoting resistance to protein misfolding in the endoplasmic reticulum.

P. Tsaytler, H. P. Harding, D. Ron, A. Bertolotti, Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332, 91–94 (2011). [Abstract] [Full Text]

R. L. Wiseman, J. W. Kelly, Phosphatase inhibition delays translational recovery. Science 332, 44–45 (2011). [Abstract] [Full Text]

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