ArticleThe Journal of biological chemistry2015
Combination of Correctors Rescue ΔF508-CFTR by Reducing Its Association with Hsp40 and Hsp27.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Pathogenic Pathways and Therapeutic Strategies in Autosomal Dominant Polycystic Kidney Disease (ADPKD).Journal of cellular signaling · 2025Article
- Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor.Molecules (Basel, Switzerland) · 2024Review
- ER-associated degradation in cystinosis pathogenesis and the prospects of precision medicine.The Journal of clinical investigation · 2023Article
- CFTR and PC2, partners in the primary cilia in autosomal dominant polycystic kidney disease.American journal of physiology. Cell physiology · 2023Article
- Ameliorating liver disease in an autosomal recessive polycystic kidney disease mouse model.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Additive Potentiation of R334W-CFTR Function by Novel Small Molecules.Journal of personalized medicine · 2023Article
- Advances in Preclinical In Vitro Models for the Translation of Precision Medicine for Cystic Fibrosis.Journal of personalized medicine · 2022Review
- Article
- The Mitochondrial CaCell calcium · 2022Article
- VX-809 mitigates disease in a mouse model of autosomal dominant polycystic kidney disease bearing the R3277C human mutation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast.G3 (Bethesda, Md.) · 2021Article
- Small Hsps as Therapeutic Targets of Cystic Fibrosis Transmembrane Conductance Regulator Protein.International journal of molecular sciences · 2021Review
- Cystic Fibrosis Lung Disease in the Aging Population.Frontiers in pharmacology · 2021Review
- Pharmacological Modulation of Ion Channels for the Treatment of Cystic Fibrosis.Journal of experimental pharmacology · 2021Review
- Effect of apical chloride concentration on the measurement of responses to CFTR modulation in airway epithelia cultured from nasal brushings.Physiological reports · 2020Article
- Article
- Transduction of Surface and Basal Cells in Rhesus Macaque Lung Following Repeat Dosing with AAV1CFTR.Human gene therapy · 2020Article
- Phosphorylation of the Chaperone-Like HspB5 Rescues Trafficking and Function of F508del-CFTR.International journal of molecular sciences · 2020Article
- A new role for heat shock factor 27 in the pathophysiology ofAmerican journal of physiology. Gastrointestinal and liver physiology · 2020Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Correcting the processing of ΔF508-CFTR, the most common mutation in cystic fibrosis, is the major goal in the development of new therapies for this disease. Here, we determined whether ΔF508 could be rescued by a combination of small-molecule correctors, and identified the mechanism by which correctors rescue the trafficking mutant of cystic fibrosis transmembrane conductance regulator (CFTR). We transfected COS-7 cells with ΔF508, created HEK-293 stably expressing ΔF508, and utilized CFBE41o(-) cell lines stably transduced with ΔF508. As shown previously, ΔF508 expressed less protein, was unstable at physiological temperature, and rapidly degraded. When the cells were treated with the combination C18 + C4 the mature C-band was expressed at the cell surface. After treatment with C18 + C4, we saw a lower rate of protein disappearance after translation was stopped with cycloheximide. To understand how this rescue occurs, we evaluated the change in the binding of proteins involved in endoplasmic reticulum-associated degradation, such as Hsp27 (HspB1) and Hsp40 (DnaJ). We saw a dramatic reduction in binding to heat shock proteins 27 and 40 following combined corrector therapy. siRNA experiments confirmed that a reduction in Hsp27 or Hsp40 rescued CFTR in the ΔF508 mutant, but the rescue was not additive or synergistic with C4 + 18 treatment, indicating these correctors shared a common pathway for rescue involving a network of endoplasmic reticulum-associated degradation proteins.
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