ABCMdb

PMID: 23071149

Okiyoneda T, Lukacs GL
Fixing cystic fibrosis by correcting CFTR domain assembly.
J Cell Biol. 2012 Oct 15;199(2):199-204. doi: 10.1083/jcb.201208083., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Arg553* ABCC7 p.Gly542* Class I mutations include nonsense mutations (G542X and R553X), generating premature termination codons and frame-shift mutations that lead to truncated and/or and nonfunctional protein (Fig. 1). Login to comment 20 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His Class III (e.g., G551D, 4%) and class IV (e.g., R117H) mutations impair the CFTR channel opening-closing (or gating) cycle and conductance, respectively, without recognizable conformational or trafficking defects. Login to comment 26 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp Efforts to correct the basic defects of CFTR biogenesis and function have been primarily focused on the most prevalent mutations: F508, G551D, and premature termination codons (Fig. 1). Login to comment 45 ABCC7 p.Gly542* (A) Class I mutations (e.g., G542X) impair production of CFTR full-length protein by induction of premature termination codons (PTC). Login to comment 50 ABCC7 p.Gly551Asp (C) Class III mutations (e.g., G551D) do not affect CFTR biosynthesis and PM expression, but impair the channel gating. Login to comment 58 ABCC7 p.Gly551Asp The most promising potentiator, VX-770 (Ivacaftor), isolated by Vertex Pharmaceuticals, Inc., restores G551D-CFTR activity to 50% of wild-type level (Van Goor et al., 2009). Login to comment 75 ABCC7 p.Arg1070Trp Stabilization of the NBD1-MSD2 interface by second site suppressor mutations (e.g., R1070W) largely restored the WT-like coupling efficiency between NBD1 stability and F508-CFTR folding (Rabeh et al., 2012). Login to comment 88 ABCC7 p.Arg1070Trp Likewise, reversing the NBD1-MSD2 interface instability by second site mutations (e.g., R1070W) only marginally rescued the F508-CFTR phenotype (Fig. 2 B). Login to comment 95 ABCC7 p.Gly551Asp Ivacaftor is the first FDA-approved drug for treatment of G551D-CFTR patients (4% of CF population), representing a landmark translational achievement, exploiting the basic biology of CFTR and years of research and development in both academia and industry. Login to comment 164 ABCC7 p.Val510Asp The V510D suppressor mutation stabilizes DeltaF508-CFTR at the cell surface. Login to comment 166 ABCC7 p.Val510Asp The V510D suppressor mutation stabilizes DeltaF508-CFTR at the cell surface. Login to comment 260 ABCC7 p.Gly551Asp Phenylglycine and sulfonamide correctors of defective delta F508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Login to comment 264 ABCC7 p.Gly551Asp Phenylglycine and sulfonamide correctors of defective delta F508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Login to comment 273 ABCC7 p.Gly551Asp A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. Login to comment 277 ABCC7 p.Gly551Asp A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. Login to comment 285 ABCC7 p.Trp1282* 2007. Restoration of W1282X CFTR activity by enhanced expression. Login to comment 290 ABCC7 p.Trp1282* 2007. Restoration of W1282X CFTR activity by enhanced expression. Login to comment