ArticleHuman molecular genetics2012
Disruption of cytokeratin-8 interaction with F508del-CFTR corrects its functional defect.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Acting on the CFTR Membrane-Spanning Domains Interface Rescues Some Misfolded Mutants.International journal of molecular sciences · 2022Article
- The Adhesion G-Protein-Coupled Receptor GPR115/Cells · 2022Article
- Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.Cellular and molecular life sciences : CMLS · 2022Article
- Systemic bis-phosphinic acid derivative restores chloride transport in Cystic Fibrosis mice.Scientific reports · 2022Article
- Recent Strategic Advances in CFTR Drug Discovery: An Overview.International journal of molecular sciences · 2020Review
- Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine.Frontiers in pharmacology · 2019Review
- Article
- Speeding Up the Identification of Cystic Fibrosis Transmembrane Conductance Regulator-Targeted Drugs: An Approach Based on Bioinformatics Strategies and Surface Plasmon Resonance.Molecules (Basel, Switzerland) · 2018Article
- Strategies for the etiological therapy of cystic fibrosis.Cell death and differentiation · 2017Review
- Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis.United European gastroenterology journal · 2017Review
- New insights into interactions between the nucleotide-binding domain of CFTR and keratin 8.Protein science : a publication of the Protein Society · 2017Article
- Structural Dynamics of the Vimentin Coiled-coil Contact Regions Involved in Filament Assembly as Revealed by Hydrogen-Deuterium Exchange.The Journal of biological chemistry · 2016Article
- Rationalising the role of Keratin 9 as a biomarker for Alzheimer's disease.Scientific reports · 2016Article
- Hallmarks of therapeutic management of the cystic fibrosis functional landscape.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Review
- Finding new drugs to enhance anion secretion in cystic fibrosis: Toward suitable systems for better drug screening. Report on the pre-conference meeting to the 12th ECFS Basic Science Conference, Albufeira, 25-28 March 2015.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Article
- An unexpected effect of TNF-α on F508del-CFTR maturation and function.F1000Research · 2015Article
- Article
- Discovery of novel potent ΔF508-CFTR correctors that target the nucleotide binding domain.EMBO molecular medicine · 2013Article
- Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.PloS one · 2013Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
We have previously reported an increased expression of cytokeratins 8/18 (K8/K18) in cells expressing the F508del mutation of cystic fibrosis transmembrane conductance regulator (CFTR). This is associated with increased colocalization of CFTR and K18 in the vicinity of the endoplasmic reticulum, although this is reversed by treating cells with curcumin, resulting in the rescue of F508del-CFTR. In the present work, we hypothesized that (i) the K8/K18 network may interact physically with CFTR, and that (ii) this interaction may modify CFTR function. CFTR was immunoprecipitated from HeLa cells transfected with either wild-type (WT) CFTR or F508del-CFTR. Precipitates were subjected to 2D-gel electrophoresis and differential spots identified by mass spectrometry. K8 and K18 were found significantly increased in F508del-CFTR precipitates. Using surface plasmon resonance, we demonstrate that K8, but not K18, binds directly and preferentially to the F508del over the WT human NBD1 (nucleotide-binding domain-1). In vivo K8 interaction with F508del-CFTR was confirmed by proximity ligation assay in HeLa cells and in primary cultures of human respiratory epithelial cells. Ablation of K8 expression by siRNA in F508del-expressing HeLa cells led to the recovery of CFTR-dependent iodide efflux. Moreover, F508del-expressing mice topically treated with K8-siRNA showed restored nasal potential difference, equivalent to that of WT mice. These results show that disruption of F508del-CFTR and K8 interaction leads to the correction of the F508del-CFTR processing defect, suggesting a novel potential therapeutic target in CF.
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