Abstract
To gain insight into the proteins potentially involved in the low temperature-induced F508del-CFTR rescue process, we have explored by two-dimensional electrophoresis (2DE) the proteome of BHK cell lines expressing wt or F508del-CFTR, grown at 37 degrees C or 26 degrees C/24 h or 26 degrees C/48 h followed by 3 h of metabolic labelling with [S-35]-methionine. A set of 139 protein spots (yielding 125 mass spectrometry identifications) was identified as differentially expressed (p ANOVA<0.05) among the six phenotypic groups analysed. The data analysis suggests that the unfolded protein response (UPR) induction and some cell-metabolism repression are the major cold-shock responses that may generate a favourable cellular environment to promote F508del-CFTR rescue. Down-regulation of proteasome regulatory PA28 and/or COP9 signalosome subunit, both involved in CFTR degradation, could also be a relevant cold-shock-induced condition for F508de-CFTR rescue. Moreover, cold-shock may promote the reestablishment of some proteostasis imbalance associated with over-expression of F508del-CFTR. In B14K-F508del cells, the deregulation of RACK1, a protein described to be important for stable expression of CFTR in the plasma membrane, is partially repaired after low temperature treatment. Together these findings give new insights about F508del-CFTR rescue by low temperature treatment and the proteins involved could ultimately constitute potential therapeutic targets in CF disease
Original language | Unknown |
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Pages (from-to) | 218-230 |
Journal | Journal of Proteomics |
Volume | 73 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Jan 2009 |