Correcting temperature-sensitive protein folding defects

C. Randell Brown, Ly Q. Hong-Brown, William J. Welch

Research output: Contribution to journalArticlepeer-review

154 Scopus citations

Abstract

Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperature-sensitive protein folding defect associated with the ΔF508 cystic fibrosis transmembrane regulator (CFTR) protein. Here we examined whether the folding of other proteins which exhibit temperature- sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60(src), or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5°C) in the presence of glycerol, trimethylamine N-oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5°C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases.

Original languageEnglish (US)
Pages (from-to)1432-1444
Number of pages13
JournalJournal of Clinical Investigation
Volume99
Issue number6
DOIs
StatePublished - Mar 15 1997

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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