ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2016
CFTR Controls the Activity of NF-κB by Enhancing the Degradation of TRADD.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Studying Peripheral Neuropathy and Associated Neuropathic Pain in HIV-1 Transgenic Rats: Evaluation of the Therapeutic Effect of Cannabidiol and Beta-Caryophyllene.Pharmaceutics · 2026Article
- PM2.5 toxin benzo[a]pyrene induces life-limiting inflammation and oxidative stress in the airway by up-regulation of TRPC6 and inactivation of β2AR/CFTR signaling.bioRxiv : the preprint server for biology · 2026Article
- Genetic and chemical correction of cystic fibrosis reduces airway susceptibility to SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- The Dual Role of TRADD in Liver Disease: From Cell Death Regulation to Inflammatory Microenvironment Remodeling.International journal of molecular sciences · 2025Review
- Increased NFAT and NFκB signalling contribute to the hyperinflammatory phenotype in response to Aspergillus fumigatus in a mouse model of cystic fibrosis.PLoS pathogens · 2025Article
- From CFTR to a CF signalling network: a systems biology approach to study Cystic Fibrosis.BMC genomics · 2024Article
- Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 spike protein.Scientific reports · 2024Article
- Modulation of Plasmatic Matrix Metalloprotease 9: A Promising New Tool for Understanding the Variable Clinical Responses of Patients with Cystic Fibrosis to Cystic Fibrosis Transmembrane Conductance Regulator Modulators.International journal of molecular sciences · 2023Article
- SARS-CoV-2 Infection in Patients with Cystic Fibrosis: What We Know So Far.Life (Basel, Switzerland) · 2022Review
- CFTR and Gastrointestinal Cancers: An Update.Journal of personalized medicine · 2022Review
- Common cardiac medications potently inhibit ACE2 binding to the SARS-CoV-2 Spike, and block virus penetration and infectivity in human lung cells.Scientific reports · 2021Article
- The Interplay between the Unfolded Protein Response, Inflammation and Infection in Cystic Fibrosis.Cells · 2021Review
- Role of Mitochondria in Viral Infections.Life (Basel, Switzerland) · 2021Review
- Impairment in inflammasome signaling by the chronic Pseudomonas aeruginosa isolates from cystic fibrosis patients results in an increase in inflammatory response.Cell death & disease · 2021Article
- ABCC7/CFTR Expression Is Associated with the Clinical Course of Ulcerative Colitis Patients.Gastroenterology research and practice · 2021Article
- Enhanced Expression of Human Epididymis Protein 4 (HE4) Reflecting Pro-Inflammatory Status Is Regulated by CFTR in Cystic Fibrosis Bronchial Epithelial Cells.Frontiers in pharmacology · 2021Article
- Bone Cells Differentiation: How CFTR Mutations May Rule the Game of Stem Cells Commitment?Frontiers in cell and developmental biology · 2021Review
- Are cystic fibrosis mutation carriers a potentially highly vulnerable group to COVID-19?Journal of cellular and molecular medicine · 2020Article
- Vasculitis in Cystic Fibrosis.Frontiers in pediatrics · 2020Review
- Autophagy, Unfolded Protein Response and Lung Disease.Current research in cell biology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsChronic lung infection in cystic fibrosis leads to an inflammatory response that persists because of the chronic presence of bacteria and ultimately leads to a catastrophic failure of lung function.
methodsWe use a combination of biochemistry, cell and molecular biology to study the interaction of TRADD, a key adaptor molecule in TNFα signaling, with CFTR in the regulation of NFκB.
resultsWe show that Wt CFTR binds to and colocalizes with TRADD. TRADD is a key signaling intermediate connecting TNFα with activation of NFκB. By contrast, ΔF508 CFTR does not bind to TRADD. NF-κB activation is higher in CFBE expressing ΔF508 CFTR than in cells expressing Wt CFTR. However, this differential effect is abolished when TRADD levels are knocked down. Transfecting Wt CFTR into CFBE cells reduces NF-κB activity. However the reduction is abolished by the CFTR chloride transport inhibitor-172. Consistently, transfecting in the correctly trafficked CFTR conduction mutants G551D or S341A also fail to reduce NFκB activity. Thus CFTR must be functional if it is to regulate NF-κB activity. We also found that TNFα produced a greater increase in NF-κB activity in CFBE cells than in the same cell when Wt CFTR-corrected. Consistently, the effect is also abolished when TRADD is knocked down by shRNA. Thus, Wt CFTR control of TRADD modulates the physiological activation of NF-κB by TNFα. Based on studies with proteosomal and lysosomal inhibitors, the mechanism by which Wt CFTR, but not ΔF508 CFTR, suppresses TRADD is by lysosomal degradation.
conclusionWe have uncovered a novel mechanism whereby Wt CFTR regulates TNFα signaling by enhancing TRADD degradation. Thus by reducing the levels of TRADD, Wt CFTR suppresses downstream proinflammatory NFκB signaling. By contrast, suppression of NF-κB activation fails in CF cells expressing 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.