期刊
CHEMISTRY & BIOLOGY
卷 16, 期 5, 页码 520-530出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2009.04.005
关键词
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资金
- CCFF
- CIHR
- Cystic Fibrosis Foundation Therapeutics
- Science Foundation for providing purified CFTR modulator compounds
The cystic fibrosis (CF)-causing mutant, deltaF508-CFTR, is misfolded and fails to traffic out of the endoplasmic reticulum (ER) to the cell surface. Introduction of second site mutations that disrupt a diarginine (RXR)-based ER retention motif in the first nucleotide binding domain rescues the trafficking defect of deltaF508-CFTR, supporting a role for these motifs in mediating ER retention of the major mutant. To determine if these RXR motifs mediate retention of the native deltaF508-CFTR protein in situ, we generated peptides that mimic these motifs and should antagonize mistrafficking mediated via their aberrant exposure. Here we show robust rescue of deltaF508-CFTR in cell lines and in respiratory epithelial tissues by transduction of RXR motif-mimetics, showing that abnormal accessibility of this motif is a key determinant of mistrafficking of the major CF-causing mutant.
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