Signal Transduction

When a Half-Life Isn't

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Science  16 Aug 2013:
Vol. 341, Issue 6147, pp. 696
DOI: 10.1126/science.341.6147.696-c

A common tactic for measuring the rate of turnover of proteins in cells is to block the synthesis of new proteins by treating the cells with cyclohexamide, a drug that gums up the ribosomal assembly line that churns out proteins. But Dai et al. warn that this methodology only works if cycloheximide treatment does not itself affect the rate of protein degradation. Cells are autonomously regulated machines; as such, they can detect environmental insults and launch a stress response. In human embryonic kidney cells, the authors found that inhibiting protein synthesis with cyclohexamide led to the activation of the protein kinase AKT (also called protein kinase B). Among the many targets of AKT are the ubiquitin ligases MDM2 and Skp2. These enzymes promote protein degradation, and phosphorylation by AKT stimulates their activity. Thus, at least for certain proteins, inhibiting protein synthesis can increase the rate of protein degradation.

J. Biol. Chem. 288, 10.1074/jbc.M112.445148 (2013).

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