ArticlePloS one2015
ΔF508 CFTR surface stability is regulated by DAB2 and CHIP-mediated ubiquitination in post-endocytic compartments.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 28 citations in OpenAlex.
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Lumacaftor inhibits channel activity of rescued F508del cystic fibrosis transmembrane conductance regulator.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Targeting ubiquitination machinery in cystic fibrosis: Where do we stand?Cellular and molecular life sciences : CMLS · 2024Review
- Cell type-specific regulation of CFTR trafficking-on the verge of progress.Frontiers in cell and developmental biology · 2024Review
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Review
- The Interplay between the Unfolded Protein Response, Inflammation and Infection in Cystic Fibrosis.Cells · 2021Review
- Ubiquitination of disease-causing CFTR variants in a microsome-based assay.Analytical biochemistry · 2020Article
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitylation as a Novel Pharmaceutical Target for Cystic Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Regulation of CFTR Biogenesis by the Proteostatic Network and Pharmacological Modulators.International journal of molecular sciences · 2020Review
- Bioactive Thymosin Alpha-1 Does Not Influence F508del-CFTR Maturation and Activity.Scientific reports · 2019Article
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- Molecular basis of cystic fibrosis: from bench to bedside.Annals of translational medicine · 2018Review
- Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase.Developmental cell · 2018Article
- The Autophagy Inhibitor Spautin-1 Antagonizes Rescue of Mutant CFTR Through an Autophagy-Independent and USP13-Mediated Mechanism.Frontiers in pharmacology · 2018Article
- Peripheral Protein Quality Control as a Novel Drug Target for CFTR Stabilizer.Frontiers in pharmacology · 2018Review
- Toward inclusive therapy with CFTR modulators: Progress and challenges.Pediatric pulmonology · 2017Review
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae.American journal of physiology. Lung cellular and molecular physiology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The ΔF508 mutant form of the cystic fibrosis transmembrane conductance regulator (ΔF508 CFTR) that is normally degraded by the ER-associated degradative pathway can be rescued to the cell surface through low-temperature (27°C) culture or small molecular corrector treatment. However, it is unstable on the cell surface, and rapidly internalized and targeted to the lysosomal compartment for degradation. To understand the mechanism of this rapid turnover, we examined the role of two adaptor complexes (AP-2 and Dab2) and three E3 ubiquitin ligases (c-Cbl, CHIP, and Nedd4-2) on low-temperature rescued ΔF508 CFTR endocytosis and degradation in human airway epithelial cells. Our results demonstrate that siRNA depletion of either AP-2 or Dab2 inhibits ΔF508 CFTR endocytosis by 69% and 83%, respectively. AP-2 or Dab2 depletion also increases the rescued protein half-life of ΔF508 CFTR by ~18% and ~91%, respectively. In contrast, the depletion of each of the E3 ligases had no effect on ΔF508 CFTR endocytosis, whereas CHIP depletion significantly increased the surface half-life of ΔF508 CFTR. To determine where and when the ubiquitination occurs during ΔF508 CFTR turnover, we monitored the ubiquitination of rescued ΔF508 CFTR during the time course of CFTR endocytosis. Our results indicate that ubiquitination of the surface pool of ΔF508 CFTR begins to increase 15 min after internalization, suggesting that CFTR is ubiquitinated in a post-endocytic compartment. This post-endocytic ubiquination of ΔF508 CFTR could be blocked by either inhibiting endocytosis, by siRNA knockdown of CHIP, or by treating cells with the CFTR corrector, VX-809. Our results indicate that the post-endocytic ubiquitination of CFTR by CHIP is a critical step in the peripheral quality control of cell surface ΔF508 CFTR.
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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.