کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1226201 | 968285 | 2009 | 13 صفحه PDF | دانلود رایگان |
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 °C or 26 °C/24 h or 26 °C/48 h followed by 3 h of metabolic labelling with [35S]-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.
The cold-shock-induced cellular environment that is favourable to the (partial) rescue of F508del-CFTR processing and trafficking to the cell surface is mainly characterised by cell-metabolism reduction and unfolded protein response (UPR) activation.Figure optionsDownload as PowerPoint slide
Journal: Journal of Proteomics - Volume 73, Issue 2, 1 December 2009, Pages 218–230