Low temperature restoring effect on F508del-CFTR misprocessing: A proteomic approach

J Proteomics. 2009 Dec 1;73(2):218-30. doi: 10.1016/j.jprot.2009.09.001. Epub 2009 Sep 21.


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/24h or 26 degrees C/48h followed by 3h of metabolic labelling with [(35)S]-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 BHK-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Line
  • Cold Temperature*
  • Cricetinae
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Frameshift Mutation*
  • GTP-Binding Proteins
  • Gene Expression Regulation
  • Humans
  • Neoplasm Proteins
  • Proteomics / methods*
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Stress, Physiological


  • Neoplasm Proteins
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • GTP-Binding Proteins