ArticleAmerican journal of respiratory cell and molecular biology2010
Functional stability of rescued delta F508 cystic fibrosis transmembrane conductance regulator in airway epithelial cells.
Article in American journal of respiratory cell and molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype.Clinical pharmacology and therapeutics · 2014Guideline
- Nanohybridization as a Route to a Water-Friendly Therapeutic Tool for Rescuing Misfolded Proteins.ACS nanoscience Au · 2026Article
- Molecular Dynamics and Theratyping in Airway and Gut Organoids Reveal R352Q-CFTR Conductance Defect.American journal of respiratory cell and molecular biology · 2022Article
- Downregulation of epithelial sodium channel (ENaC) activity in human airway epithelia after low temperature incubation.BMJ open respiratory research · 2021Article
- CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathway degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Short-term consequences of F508del-CFTR thermal instability on CFTR-dependent transepithelial currents in human airway epithelial cells.Scientific reports · 2019Article
- Rapid therapeutic advances in CFTR modulator science.Pediatric pulmonology · 2018Review
- Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for limb-girdle muscular dystrophy 2D.Human molecular genetics · 2018Article
- Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell.Nature communications · 2017Article
- A synonymous codon change alters the drug sensitivity of ΔF508 cystic fibrosis transmembrane conductance regulator.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis.PloS one · 2016Article
- Capturing the Direct Binding of CFTR Correctors to CFTR by Using Click Chemistry.Chembiochem : a European journal of chemical biology · 2015Article
- Functional and pharmacological induced structural changes of the cystic fibrosis transmembrane conductance regulator in the membrane solved using SAXS.Cellular and molecular life sciences : CMLS · 2015Article
- PharmGKB summary: very important pharmacogene information for CFTR.Pharmacogenetics and genomics · 2015Article
- Rescuing ΔF508 CFTR with trimethylangelicin, a dual-acting corrector and potentiator.American journal of physiology. Lung cellular and molecular physiology · 2014Review
- Stabilizing rescued surface-localized δf508 CFTR by potentiation of its interaction with Na(+)/H(+) exchanger regulatory factor 1.Biochemistry · 2014Article
- The silent codon change I507-ATC->ATT contributes to the severity of the ΔF508 CFTR channel dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Cystic fibrosis transmembrane regulator correctors and potentiators.Cold Spring Harbor perspectives in medicine · 2013Review
- Regulated recycling of mutant CFTR is partially restored by pharmacological treatment.Journal of cell science · 2013Article
- Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The most common mutation in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene, Delta F508, results in the production of a misfolded protein that is rapidly degraded. The mutant protein is temperature sensitive, and prior studies indicate that the low-temperature-rescued channel is poorly responsive to physiological stimuli, and is rapidly degraded from the cell surface at 37 degrees C. In the present studies, we tested the effect of a recently characterized pharmacological corrector, 2-(5-chloro-2-methoxy-phenylamino)-4'-methyl-[4,5'bithiazolyl-2'-yl]-phenyl-methanone (corr-4a), on cell surface stability and function of the low-temperature-rescued Delta F508 CFTR. We demonstrate that corr-4a significantly enhanced the protein stability of rescued Delta F508 CFTR for up to 12 hours at 37 degrees C (P < 0.05). Using firefly luciferase-based reporters to investigate the mechanisms by which low temperature and corr-4a enhance rescue, we found that low-temperature treatment inhibited proteasomal function, whereas corr-4a treatment inhibited the E1-E3 ubiquitination pathway. Ussing chamber studies indicated that corr-4a increased the cAMP-mediated Delta F508 CFTR response by 61% at 6 hours (P < 0.05), but not at later time points. However, addition of the CFTR channel activator, 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol, significantly augmented cAMP-stimulated currents, revealing that the biochemically detectable cell surface Delta F508 CFTR could be stimulated under the right conditions. Our studies demonstrate that stabilizing rescued Delta F508 CFTR was not sufficient to obtain maximal Delta F508 CFTR function in airway epithelial cells. These results strongly support the idea that maximal correction of Delta F508 CFTR requires a chemical corrector that: (1) promotes folding and exit from the endoplasmic reticulum; (2) enhances surface stability; and (3) improves channel activity.
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Registered trials
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