ArticleThe Biochemical journal2008
Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones.
Article in The Biochemical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 101 citations in OpenAlex.
- Article
- Recommended Tool Compounds for Modifying the Cystic Fibrosis Transmembrane Conductance Regulator Channel Variants.ACS pharmacology & translational science · 2024Review
- Pharmacological rescue of the G85E CFTR variant by preclinical and approved modulators.Frontiers in pharmacology · 2024Article
- Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.Frontiers in pediatrics · 2024Review
- YES1 Kinase Mediates the Membrane Removal of Rescued F508del-CFTR in Airway Cells by Promoting MAPK Pathway Activation via SHC1.Biomolecules · 2023Article
- Phenotypic Alteration of an Established Human Airway Cell Line by Media Selection.International journal of molecular sciences · 2023Article
- Additive Potentiation of R334W-CFTR Function by Novel Small Molecules.Journal of personalized medicine · 2023Article
- Article
- NBD2 Is Required for the Rescue of Mutant F508del CFTR by a Thiazole-Based Molecule: A Class II Corrector for the Multi-Drug Therapy of Cystic Fibrosis.Biomolecules · 2021Article
- Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment.International journal of molecular sciences · 2021Article
- Positional effects of premature termination codons on the biochemical and biophysical properties of CFTR.The Journal of physiology · 2020Article
- Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting.Journal of cell science · 2019Article
- Hsp70 and DNAJA2 limit CFTR levels through degradation.PloS one · 2019Article
- Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase.Developmental cell · 2018Article
- Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer.Frontiers in pharmacology · 2018Review
- Analysis of cystic fibrosis-associated P67L CFTR illustrates barriers to personalized therapeutics for orphan diseases.JCI insight · 2016Article
- Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance.Clinics in chest medicine · 2016Review
- CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis.Reviews of physiology, biochemistry and pharmacology · 2016Review
- Article
- Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives.Clinical pharmacology : advances and applications · 2016Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Misfolded proteins destined for the cell surface are recognized and degraded by the ERAD [ER (endoplasmic reticulum) associated degradation] pathway. TS (temperature-sensitive) mutants at the permissive temperature escape ERAD and reach the cell surface. In this present paper, we examined a TS mutant of the CFTR [CF (cystic fibrosis) transmembrane conductance regulator], CFTR DeltaF508, and analysed its cell-surface trafficking after rescue [rDeltaF508 (rescued DeltaF508) CFTR]. We show that rDeltaF508 CFTR endocytosis is 6-fold more rapid (approximately 30% per 2.5 min) than WT (wild-type, approximately 5% per 2.5 min) CFTR at 37 degrees C in polarized airway epithelial cells (CFBE41o-). We also investigated rDeltaF508 CFTR endocytosis under two further conditions: in culture at the permissive temperature (27 degrees C) and following treatment with pharmacological chaperones. At low temperature, rDeltaF508 CFTR endocytosis slowed to WT rates (20% per 10 min), indicating that the cell-surface trafficking defect of rDeltaF508 CFTR is TS. Furthermore, rDeltaF508 CFTR is stabilized at the lower temperature; its half-life increases from <2 h at 37 degrees C to >8 h at 27 degrees C. Pharmacological chaperone treatment at 37 degrees C corrected the rDeltaF508 CFTR internalization defect, slowing endocytosis from approximately 30% per 2.5 min to approximately 5% per 2.5 min, and doubled DeltaF508 surface half-life from 2 to 4 h. These effects are DeltaF508 CFTR-specific, as pharmacological chaperones did not affect WT CFTR or transferrin receptor internalization rates. The results indicate that small molecular correctors may reproduce the effect of incubation at the permissive temperature, not only by rescuing DeltaF508 CFTR from ERAD, but also by enhancing its cell-surface stability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.