Targets for cystic fibrosis therapy: proteomic analysis and correction of mutant cystic fibrosis transmembrane conductance regulator

References

• Riordan JR. CFTR function and prospects for therapy. Annu. Rev. Biochem.77, 701–726 (2008).
   PubMed Web of Science ®Google Scholar
• Quinton PM. Chloride impermeability in cystic fibrosis. Nature301(5899), 421–422 (1983).
   PubMed Web of Science ®Google Scholar
• Quinton PM, Bijman J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. N. Engl. J. Med.308(20), 1185–1189 (1983).
   PubMedGoogle Scholar
• Riordan JR, Rommens JM, Kerem B et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science245(4922), 1066–1073 (1989).
   PubMed Web of Science ®Google Scholar
• Griesenbach U, Alton EW. Cystic fibrosis gene therapy: successes, failures and hopes for the future. Expert Rev. Respir. Med.3(4), 363–371 (2009).
   PubMedGoogle Scholar
• Amaral MD, Kunzelmann K. Molecular targeting of CFTR as a therapeutic approach to cystic fibrosis. Trends Pharmacol. Sci.28(7), 334–341 (2007).
   PubMed Web of Science ®Google Scholar
• Cheng SH, Gregory RJ, Marshall J et al. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell63(4), 827–834 (1990).
   PubMed Web of Science ®Google Scholar
• Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell83(1), 129–135 (1995).
   PubMed Web of Science ®Google Scholar
• Ward CL, Omura S, Kopito RR. Degradation of CFTR by the ubiquitin–proteasome pathway. Cell83(1), 121–127 (1995).
   PubMed Web of Science ®Google Scholar
• Younger JM, Chen L, Ren HY et al. Sequential quality-control checkpoints triage misfolded cystic fibrosis transmembrane conductance regulator. Cell126(3), 571–582 (2006).
   PubMed Web of Science ®Google Scholar
• Denning GM, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature358(6389), 761–764 (1992).
   PubMed Web of Science ®Google Scholar
• Roy G, Chalfin EM, Saxena A, Wang X. Interplay between ER exit code and domain conformation in CFTR misprocessing and rescue. Mol. Biol. Cell21(4), 597–609 (2010).
   PubMedGoogle Scholar
• Chang XB, Cui L, Hou YX et al. Removal of multiple arginine-framed trafficking signals overcomes misprocessing of Δ F508 CFTR present in most patients with cystic fibrosis. Mol. Cell4(1), 137–142 (1999).
   PubMedGoogle Scholar
• Wang X, Matteson J, An Y et al. COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. J. Cell Biol.167(1), 65–74 (2004).
   PubMed Web of Science ®Google Scholar
• Teem JL, Berger HA, Ostedgaard LS, Rich DP, Tsui LC, Welsh MJ. Identification of revertants for the cystic fibrosis Δ F508 mutation using STE6–CFTR chimeras in yeast. Cell73(2), 335–346 (1993).
   PubMedGoogle Scholar
• Teem JL, Carson MR, Welsh MJ. Mutation of R555 in CFTR-D F508 enhances function and partially corrects defective processing. Receptors Channels4(1), 63–72 (1996).
   PubMedGoogle Scholar
• Hegedus T, Aleksandrov A, Cui L, Gentzsch M, Chang XB, Riordan JR. F508del CFTR with two altered RXR motifs escapes from ER quality control but its channel activity is thermally sensitive. Biochim. Biophys. Acta1758(5), 565–572 (2006).
   PubMedGoogle Scholar
• He L, Aleksandrov LA, Cui L, Jensen TJ, Nesbitt KL, Riordan JR. Restoration of domain folding and interdomain assembly by second-site suppressors of the ΔF508 mutation in CFTR. FASED J. DOI: 10.1096/fj.09-141788 (2010) (Epub ahead of print).
   Google Scholar
• Lewis HA, Zhao X, Wang C et al. Impact of the ΔF508 mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J. Biol. Chem.280(2), 1346–1353 (2005).
   PubMed Web of Science ®Google Scholar
• Du K, Sharma M, Lukacs GL. The ΔF508 cystic fibrosis mutation impairs domain–domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol.12(1), 17–25 (2005).
   PubMed Web of Science ®Google Scholar
• Cui L, Aleksandrov L, Chang XB et al. Domain interdependence in the biosynthetic assembly of CFTR. J. Mol. Biol.365(4), 981–994 (2007).
   PubMed Web of Science ®Google Scholar
• Wang X, Koulov AV, Kellner WA, Riordan JR, Balch WE. Chemical and biological folding contribute to temperature-sensitive ΔF508 CFTR trafficking. Traffic9(11), 1878–1893 (2008).
   PubMedGoogle Scholar
• Pedemonte N, Tomati V, Sondo E, Galietta LJ. Influence of cell background on pharmacological rescue of mutant CFTR. Am. J. Physiol. Cell Physiol.298(4), C866–874 (2010).
   PubMed Web of Science ®Google Scholar
• Rowe SM, Pyle LC, Jurkevante A et al. ΔF508 CFTR processing correction and activity in polarized airway and non-airway cell monolayers. Pulm. Pharmacol. Ther.23(4), 268–278 (2010).
   PubMed Web of Science ®Google Scholar
• Lukacs GL, Chang XB, Bear C et al. The Δ F508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells. J. Biol. Chem.268(29), 21592–21598 (1993).
   PubMed Web of Science ®Google Scholar
• Heda GD, Tanwani M, Marino CR. The ΔF508 mutation shortens the biochemical half-life of plasma membrane CFTR in polarized epithelial cells. Am. J. Physiol. Cell Physiol.280(1), C166–C174 (2001).
   Google Scholar
• Sharma M, Benharouga M, Hu W, Lukacs GL. Conformational and temperature-sensitive stability defects of the Δ F508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J. Biol. Chem.276(12), 8942–8950 (2001).
   PubMed Web of Science ®Google Scholar
• Gentzsch M, Chang XB, Cui L et al. Endocytic trafficking routes of wild type and ΔF508 cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell15(6), 2684–2696 (2004).
   PubMedGoogle Scholar
• Swiatecka-Urban A, Brown A, Moreau-Marquis S et al. The short apical membrane half-life of rescued ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of ΔF508-CFTR in polarized human airway epithelial cells. J. Biol. Chem.280(44), 36762–36772 (2005).
   PubMed Web of Science ®Google Scholar
• Cholon DM, O’Neal WK, Randell SH, Riordan JR, Gentzsch M. Modulation of endocytic trafficking and apical stability of CFTR in primary human airway epithelial cultures. Am. J. Physiol. Lung Cell Mol. Physiol.298(3), L304–L314 (2010).
   Google Scholar
• Sharma M, Pampinella F, Nemes C et al. Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes. J. Cell Biol.164(6), 923–933 (2004).
   PubMed Web of Science ®Google Scholar
• Varga K, Goldstein RF, Jurkuvenaite A et al. Enhanced cell-surface stability of rescued ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones. Biochem. J.410(3), 555–564 (2008).
   PubMed Web of Science ®Google Scholar
• Jurkuvenaite A, Chen L, Bartoszewski R et al. Functional stability of rescued ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells. Am. J. Respir. Cell Mol. Biol.42(3), 363–372 (2009).
   PubMedGoogle Scholar
• Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T. Dynasore, a cell-permeable inhibitor of dynamin. Dev. Cell10(6), 839–850 (2006).
   PubMed Web of Science ®Google Scholar
• Wang X, Venable J, LaPointe P et al. Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell127(4), 803–815 (2006).
   PubMed Web of Science ®Google Scholar
• Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol.19(3), 242–247 (2001).
   PubMed Web of Science ®Google Scholar
• Gomes-Alves P, Couto F, Pesquita C, Coelho AV, Penque D. Rescue of F508del-CFTR by RXR motif inactivation triggers proteome modulation associated with the unfolded protein response. Biochim. Biophys. Acta1804(4), 856–865 (2010).
   PubMed Web of Science ®Google Scholar
• Bartoszewski R, Rab A, Jurkuvenaite A et al. Activation of the unfolded protein response by ΔF508 CFTR. Am. J. Respir. Cell Mol. Biol.39(4), 448–457 (2008).
   PubMed Web of Science ®Google Scholar
• Roxo-Rosa M, Xu Z, Schmidt A et al. Revertant mutants G550E and 4RK rescue cystic fibrosis mutants in the first nucleotide-binding domain of CFTR by different mechanisms. Proc. Natl Acad. Sci. USA103(47), 17891–17896 (2006).
   PubMedGoogle Scholar
• Singh OV, Pollard HB, Zeitlin PL. Chemical rescue of ΔF508-CFTR mimics genetic repair in cystic fibrosis bronchial epithelial cells. Mol. Cell Proteomics7(6), 1099–1110 (2008).
   PubMed Web of Science ®Google Scholar
• Trzcinska-Daneluti AM, Ly D, Huynh L, Jiang C, Fladd C, Rotin D. High-content functional screen to identify proteins that correct F508del-CFTR function. Mol. Cell Proteomics8(4), 780–790 (2009).
   PubMed Web of Science ®Google Scholar
• Sato S, Ward CL, Krouse ME, Wine JJ, Kopito RR. Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J. Biol. Chem.271(2), 635–638 (1996).
   PubMed Web of Science ®Google Scholar
• Egan ME, Glockner-Pagel J, Ambrose C et al. Calcium-pump inhibitors induce functional surface expression of ΔF508-CFTR protein in cystic fibrosis epithelial cells. Nat. Med.8(5), 485–492 (2002).
   PubMed Web of Science ®Google Scholar
• Egan ME, Pearson M, Weiner SA et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science304(5670), 600–602 (2004).
   PubMed Web of Science ®Google Scholar
• Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM. Partial correction of cystic fibrosis defects with PLGA nanoparticles encapsulating curcumin. Mol. Pharm.7(1), 86–93 (2010).
   PubMed Web of Science ®Google Scholar
• Zaman K, Carraro S, Doherty J et al. S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells. Mol. Pharmacol.70(4), 1435–1442 (2006).
   PubMed Web of Science ®Google Scholar
• Zaman K, McPherson M, Vaughan J et al. S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation. Biochem. Biophys. Res. Commun.284(1), 65–70 (2001).
   PubMed Web of Science ®Google Scholar
• Rubenstein RC, Egan ME, Zeitlin PL. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing Δ F508-CFTR. J. Clin. Invest.100(10), 2457–2465 (1997).
   PubMed Web of Science ®Google Scholar
• Rubenstein RC, Zeitlin PL. Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of ΔF508-CFTR. Am. J. Physiol. Cell Physiol.278(2), C259–C267 (2000).
   PubMed Web of Science ®Google Scholar
• Lim M, McKenzie K, Floyd AD, Kwon E, Zeitlin PL. Modulation of ΔF508 cystic fibrosis transmembrane regulator trafficking and function with 4-phenylbutyrate and flavonoids. Am. J. Respir. Cell Mol. Biol.31(3), 351–357 (2004).
   PubMed Web of Science ®Google Scholar
• Pedemonte N, Lukacs GL, Du K et al. Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest.115(9), 2564–2571 (2005).
   PubMed Web of Science ®Google Scholar
• Van Goor F, Straley KS, Cao D et al. Rescue of ΔF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol. Lung Cell Mol. Physiol.290(6), L1117–L1130 (2006).
   PubMed Web of Science ®Google Scholar
• Carlile GW, Robert R, Zhang D et al. Correctors of protein trafficking defects identified by a novel high-throughput screening assay. Chembiochem.8(9), 1012–1020 (2007).
   PubMed Web of Science ®Google Scholar
• Robert R, Carlile GC, Liao J et al. Correction of ΔF508-CFTR trafficking defect by the bioavailable compound glafenine. Mol. Pharmacol. DOI: 10.1124/mol.109.062679 (2010) (Epub ahead of print).
   PubMedGoogle Scholar
• Robert R, Carlile GW, Pavel C et al. Structural analog of sildenafil identified as a novel corrector of the F508del-CFTR trafficking defect. Mol. Pharmacol.73(2), 478–489 (2008).
   PubMed Web of Science ®Google Scholar
• Ma T, Vetrivel L, Yang H et al. High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening. J. Biol. Chem.277(40), 37235–37241 (2002).
   PubMed Web of Science ®Google Scholar
• Yang H, Shelat AA, Guy RK et al. Nanomolar affinity small molecule correctors of defective ΔF508-CFTR chloride channel gating. J. Biol. Chem.278(37), 35079–35085 (2003).
   PubMed Web of Science ®Google Scholar
• Pedemonte N, Sonawane ND, Taddei A et al. Phenylglycine and sulfonamide correctors of defective Δ F508 and G551D cystic fibrosis transmembrane conductance regulator chloride-channel gating. Mol. Pharmacol.67(5), 1797–1807 (2005).
   PubMed Web of Science ®Google Scholar
• Cohen FE, Kelly JW. Therapeutic approaches to protein-misfolding diseases. Nature426(6968), 905–909 (2003).
   PubMed Web of Science ®Google Scholar
• Kerem E, Hirawat S, Armoni S et al. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective Phase II trial. Lancet372(9640), 719–727 (2008).
   PubMed Web of Science ®Google Scholar
• Frischmeyer PA, Dietz HC. Nonsense-mediated mRNA decay in health and disease. Hum. Mol. Genet.8(10), 1893–1900 (1999).
   PubMed Web of Science ®Google Scholar
• Losson R, Lacroute F. Interference of nonsense mutations with eukaryotic messenger RNA stability. Proc. Natl Acad. Sci. USA76(10), 5134–5137 (1979).
   PubMed Web of Science ®Google Scholar
• Maquat LE. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat. Rev. Mol. Cell Biol.5(2), 89–99 (2004).
   PubMed Web of Science ®Google Scholar
• Krawczak M, Ball EV, Fenton I et al. Human gene mutation database – a biomedical information and research resource. Hum. Mutat.15(1), 45–51 (2000).
   PubMed Web of Science ®Google Scholar
• Mendell JT, Dietz HC. When the message goes awry: disease-producing mutations that influence mRNA content and performance. Cell107(4), 411–414 (2001).
   PubMed Web of Science ®Google Scholar
• Fearon K, McClendon V, Bonetti B, Bedwell DM. Premature translation termination mutations are efficiently suppressed in a highly conserved region of yeast Ste6p, a member of the ATP-binding cassette (ABC) transporter family. J. Biol. Chem.269(27), 17802–17808 (1994).
   PubMed Web of Science ®Google Scholar
• Howard M, Frizzell RA, Bedwell DM. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat. Med.2(4), 467–469 (1996).
   PubMed Web of Science ®Google Scholar
• Bedwell DM, Kaenjak A, Benos DJ et al. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat. Med.3(11), 1280–1284 (1997).
   PubMed Web of Science ®Google Scholar
• Hamosh A, Trapnell BC, Zeitlin PL et al. Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis. J. Clin. Invest.88(6), 1880–1885 (1991).
   PubMedGoogle Scholar
• Bal J, Stuhrmann M, Schloesser M, Schmidtke J, Reiss J. A cystic fibrosis patient homozygous for the nonsense mutation R553X. J. Med. Genet.28(10), 715–717 (1991).
   PubMed Web of Science ®Google Scholar
• Davies J. Effects of streptomycin and related antibiotics on protein synthesis. Antimicrob. Agents Chemother. (Bethesda)5, 1001–1005 (1965).
   PubMedGoogle Scholar
• Davies J, Gorini L, Davis BD. Misreading of RNA codewords induced by aminoglycoside antibiotics. Mol. Pharmacol.1(1), 93–106 (1965).
   PubMedGoogle Scholar
• Singh A, Ursic D, Davies J. Phenotypic suppression and misreading Saccharomyces cerevisiae.Nature277(5692), 146–148 (1979).
   PubMed Web of Science ®Google Scholar
• Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL. Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J. Clin. Invest.104(4), 375–381 (1999).
   PubMed Web of Science ®Google Scholar
• Wilschanski M, Famini C, Blau H et al. A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations. Am. J. Respir. Crit. Care Med.161(3 Pt 1), 860–865 (2000).
   PubMed Web of Science ®Google Scholar
• Wilschanski M, Yahav Y, Yaacov Y et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N. Engl. J. Med.349(15), 1433–1441 (2003).
   PubMed Web of Science ®Google Scholar
• Clancy JP, Bebok Z, Ruiz F et al. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med.163(7), 1683–1692 (2001).
   PubMed Web of Science ®Google Scholar
• Du M, Jones JR, Lanier J et al. Aminoglycoside suppression of a premature stop mutation in a Cftr-/- mouse carrying a human CFTR–G542X transgene. J. Mol. Med.80(9), 595–604 (2002).
   PubMed Web of Science ®Google Scholar
• Du M, Keeling KM, Fan L et al. Clinical doses of amikacin provide more effective suppression of the human CFTR–G542X stop mutation than gentamicin in a transgenic CF mouse model. J. Mol. Med.84(7), 573–582 (2006).
   PubMed Web of Science ®Google Scholar
• Hamed SA. Drug evaluation: PTC-124 – a potential treatment of cystic fibrosis and Duchenne muscular dystrophy. IDrugs9(11), 783–789 (2006).
   PubMed Web of Science ®Google Scholar
• Du M, Liu X, Welch EM, Hirawat S, Peltz SW, Bedwell DM. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR–G542X nonsense allele in a CF mouse model. Proc. Natl Acad. Sci. USA105(6), 2064–2069 (2008).
   PubMed Web of Science ®Google Scholar
• Wilton S. PTC124, nonsense mutations and Duchenne muscular dystrophy. Neuromuscul. Disord.17(9–10), 719–720 (2007).
   PubMed Web of Science ®Google Scholar
• Hirawat S, Welch EM, Elfring GL et al. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J. Clin. Pharmacol.47(4), 430–444 (2007).
   PubMed Web of Science ®Google Scholar
• Dunant P, Walter MC, Karpati G, Lochmuller H. Gentamicin fails to increase dystrophin expression in dystrophin-deficient muscle. Muscle Nerve27(5), 624–627 (2003).
   PubMed Web of Science ®Google Scholar
• Clancy JP, Rowe SM, Bebok Z et al. No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations. Am. J. Respir. Cell Mol. Biol.37(1), 57–66 (2007).
   PubMed Web of Science ®Google Scholar
• Manuvakhova M, Keeling K, Bedwell DM. Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA6(7), 1044–1055 (2000).
   PubMed Web of Science ®Google Scholar
• Diop D, Chauvin C, Jean-Jean O. Aminoglycosides and other factors promoting stop codon readthrough in human cells. C. R. Biol.330(1), 71–79 (2007).
   PubMedGoogle Scholar
• Linde L, Kerem B. Introducing sense into nonsense in treatments of human genetic diseases. Trends Genet.24(11), 552–563 (2008).
   PubMed Web of Science ®Google Scholar
• Kultz D. Molecular and evolutionary basis of the cellular stress response. Annu. Rev. Physiol.67, 225–257 (2005).
   PubMed Web of Science ®Google Scholar
• Rutkowski DT, Kaufman RJ. A trip to the ER: coping with stress. Trends Cell Biol.14(1), 20–28 (2004).
   PubMed Web of Science ®Google Scholar
• Schroder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat. Res.569(1–2), 29–63 (2005).
   PubMed Web of Science ®Google Scholar
• Martino ME, Olsen JC, Fulcher NB, Wolfgang MC, O’Neal WK, Ribeiro CM. Airway epithelial inflammation-induced endoplasmic reticulum Ca2+ store expansion is mediated by X-box binding protein-1. J. Biol. Chem.284(22), 14904–14913 (2009).
   PubMedGoogle Scholar
• Bi M, Naczki C, Koritzinsky M et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J.24(19), 3470–3481 (2005).
   PubMed Web of Science ®Google Scholar
• Bartoszewski R, Rab A, Twitty G et al. The mechanism of cystic fibrosis transmembrane conductance regulator transcriptional repression during the unfolded protein response. J. Biol. Chem.283(18), 12154–12165 (2008).
   PubMedGoogle Scholar
• Rab A, Bartoszewski R, Jurkuvenaite A, Wakefield J, Collawn JF, Bebok Z. Endoplasmic reticulum stress and the unfolded protein response regulate genomic cystic fibrosis transmembrane conductance regulator expression. Am. J. Physiol. Cell Physiol.292(2), C756–C766 (2007).
   Google Scholar
• Jorgensen E, Stinson A, Shan L, Yang J, Gietl D, Albino AP. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells. BMC Cancer8, 229 (2008).
   PubMed Web of Science ®Google Scholar
• Cantin AM, Bilodeau G, Ouellet C, Liao J, Hanrahan JW. Oxidant stress suppresses CFTR expression. Am. J. Physiol. Cell Physiol.290(1), C262–C270 (2006).
   Google Scholar
• Cantin AM, Hanrahan JW, Bilodeau G et al. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Am. J. Respir. Crit. Care Med.173(10), 1139–1144 (2006).
   PubMed Web of Science ®Google Scholar
• Conti E, Izaurralde E. Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species. Curr. Opin. Cell Biol.17(3), 316–325 (2005).
   PubMedGoogle Scholar
• Keeling KM, Lanier J, Du M et al. Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae.RNA10(4), 691–703 (2004).
   PubMedGoogle Scholar
• Linde L, Boelz S, Neu-Yilik G, Kulozik AE, Kerem B. The efficiency of nonsense-mediated mRNA decay is an inherent character and varies among different cells. Eur. J. Hum. Genet.15(11), 1156–1162 (2007).
   PubMed Web of Science ®Google Scholar
• Linde L, Boelz S, Nissim-Rafinia M et al. Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J. Clin. Invest.117(3), 683–692 (2007).
   PubMed Web of Science ®Google Scholar
• Guimbellot JS, Fortenberry JA, Siegal GP et al. Role of oxygen availability in CFTR expression and function. Am. J. Respir. Cell Mol. Biol.39(5), 514–521 (2008).
   PubMed Web of Science ®Google Scholar
• Gardner LB. Hypoxic inhibition of nonsense-mediated RNA decay regulates gene expression and the integrated stress response. Mol. Cell Biol.28(11), 3729–3741 (2008).
   PubMed Web of Science ®Google Scholar
• Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature454(7203), 455–462 (2008).
   PubMed Web of Science ®Google Scholar
• Jones AM, Helm JM. Emerging treatments in cystic fibrosis. Drugs69(14), 1903–1910 (2009).
   PubMed Web of Science ®Google Scholar
• Van Goor F, Hadida S, Grootenhuis PD et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc. Natl Acad. Sci. USA106(44), 18825–18830 (2009).
   PubMed Web of Science ®Google Scholar
• Caohuy H, Jozwik C, Pollard HB. Rescue of ΔF508-CFTR by the SGK1/Nedd4-2 signaling pathway. J. Biol. Chem.284(37), 25241–25253 (2009).
   PubMedGoogle Scholar
• Hassink GC, Zhao B, Sompallae R et al. The ER-resident ubiquitin-specific protease 19 participates in the UPR and rescues ERAD substrates. EMBO Rep.10(7), 755–761 (2009).
   PubMed Web of Science ®Google Scholar
• Grove DE, Rosser MF, Ren HY, Naren AP, Cyr DM. Mechanisms for rescue of correctable folding defects in CFTRΔF508. Mol. Biol. Cell20(18), 4059–4069 (2009).
   PubMed Web of Science ®Google Scholar
• Zhu H, Zhu JX, Lo PS et al. Rescue of defective pancreatic secretion in cystic-fibrosis cells by suppression of a novel isoform of phospholipase C. Lancet362(9401), 2059–2065 (2003).
   PubMedGoogle Scholar
• Henderson MJ, Vij N, Zeitlin PL. Ubiquitin C-terminal hydrolase-L1 protects cystic fibrosis transmembrane conductance regulator from early stages of proteasomal degradation. J. Biol. Chem.285(15), 11314–11325 (2010).
   PubMed Web of Science ®Google Scholar
• Hutt DM, Herman D, Rodrigues AP et al. Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat. Chem. Biol.6(1), 25–33 (2010).
   PubMed Web of Science ®Google Scholar
• Cheng J, Cebotaru V, Cebotaru L, Guggino WB. Syntaxin 6 and CAL mediate the degradation of the cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell21(7), 1178–1187 (2010).
   PubMedGoogle Scholar
• Cheng J, Moyer BD, Milewski M et al. A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression. J. Biol. Chem.277(5), 3520–3529 (2002).
   PubMed Web of Science ®Google Scholar
• Wolde M, Fellows A, Cheng J et al. Targeting CAL as a negative regulator of ΔF508-CFTR cell-surface expression: an RNA interference and structure-based mutagenetic approach. J. Biol. Chem.282(11), 8099–8109 (2007).
   PubMedGoogle Scholar
• Favia M, Guerra L, Fanelli T et al. Na+/H+ exchanger regulatory factor 1 overexpression-dependent increase of cytoskeleton organization is fundamental in the rescue of F508del cystic fibrosis transmembrane conductance regulator in human airway CFBE41o- cells. Mol. Biol. Cell21(1), 73–86 (2010).
   PubMed Web of Science ®Google Scholar
• Kwon SH, Pollard H, Guggino WB. Knockdown of NHERF1 enhances degradation of temperature rescued ΔF508 CFTR from the cell surface of human airway cells. Cell Physiol. Biochem.20(6), 763–772 (2007).
   PubMedGoogle Scholar
• Cheng J, Wang H, Guggino WB. Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10. J. Biol. Chem.280(5), 3731–3739 (2005).
   PubMedGoogle Scholar