期刊
JOURNAL OF PROTEOMICS
卷 73, 期 2, 页码 218-230出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jprot.2009.09.001
关键词
F508del-CFTR; Low temperature; Protein trafficking; Therapeutic targets
资金
- FCT/FEDER [POCTI/MGI/40878/2001, POCI/SAU-MMO/56163/2004]
- FCT/Poly-Annual Funding Program
- FEDER/Sadde XXI Program (Portugal)
- FCT-PhD [SFRH/BD/17744/2004]
- Fundação para a Ciência e a Tecnologia [POCTI/MGI/40878/2001, SFRH/BD/17744/2004, POCI/SAU-MMO/56163/2004] Funding Source: FCT
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. (C) 2009 Elsevier B.V. All rights reserved.
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