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Protein degradation

Maintaining supplies

Nature Reviews Molecular Cell Biology volume 7, pages 82–83 (2006)Cite this article

The authors first established a system in which they could measure the immediate effects of proteasome inhibition in HeLa cells. They selected a rapidly degraded ubiquitin-tagged protein as a reporter of proteasome activity, and showed that the simultaneous addition of a proteasome inhibitor and an inhibitor of protein synthesis (which is known to work quickly) stabilized reporter levels. So, because the level of the reporter did not decrease, proteasome inhibition was immediate.

The effect of this immediate proteasome inhibition on protein translation was subsequently analysed under conditions of acute amino-acid restriction. Proteasome inhibition was shown to impair translation only when cells were incubated in a medium that lacked at least one essential amino acid. This indicates that the proteasome has an essential role in allowing translation to proceed when amino-acid supplies are suddenly limited. Indeed, inhibiting the proteasome during prolonged amino-acid restriction did not affect translation. Furthermore, during acute amino-acid restriction, translation was unaffected by inhibiting the autophagosomal–lysosomal pathway.

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ORIGINAL RESEARCH PAPER

  1. Vabulas, R. M. & Hartl, F. U. Protein synthesis upon acute nutrient restriction relies on proteasome function. Science 310, 1960–1963 (2005)

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  1. Rachel Smallridge
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Smallridge, R. Maintaining supplies. Nat Rev Mol Cell Biol 7, 82–83 (2006). https://doi.org/10.1038/nrm1866

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  • DOI: https://doi.org/10.1038/nrm1866

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