A novel approach to recovery of function of mutant proteins by slowing down translation

Anatoli B. Meriin, Martin Mense, Jeff D. Colbert, Feng Liang, Hermann Bihler, Nava Zaarur, Kenneth L. Rock, Michael Y. Sherman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Protein homeostasis depends on a balance of translation, folding, and degradation. Here, we demonstrate that mild inhibition of translation results in a dramatic and disproportional reduction in production of misfolded polypeptides in mammalian cells, suggesting an improved folding of newly synthesized proteins. Indeed, inhibition of translation elongation, which slightly attenuated levels of a copepod GFP mutant protein, significantly enhanced its function. In contrast, inhibition of translation initiation had minimal effects on copepod GFP folding. On the other hand, mild suppression of either translation elongation or initiation corrected folding defects of the disease-associated cystic fibrosis transmembrane conductance regulator mutant F508del. We propose that modulation of translation can be used as a novel approach to improve overall proteostasis in mammalian cells, as well as functions of disease-associated mutant proteins with folding deficiencies.

Original languageEnglish
Pages (from-to)34264-34272
Number of pages9
JournalJournal of Biological Chemistry
Issue number41
StatePublished - 5 Oct 2012
Externally publishedYes


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