ArticleMolecular & cellular proteomics : MCP2015
RNA Interference Screen to Identify Kinases That Suppress Rescue of ΔF508-CFTR.
Article in Molecular & cellular proteomics : MCP, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and ΔF508-CFTR rescue.Scientific reports · 2020Pooled it
- Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells.Respiratory research · 2024Article
- A novel role for CFTR interaction with LH and FGF in azoospermia and epididymal maldevelopment caused by cryptorchidism.Basic and clinical andrology · 2022Review
- Targeting the EGFR-ERK axis using the compatible solute ectoine to stabilize CFTR mutant F508del.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform.CPT: pharmacometrics & systems pharmacology · 2022Article
- Dual Blockade of Misfolded Alpha-Sarcoglycan Degradation by Bortezomib and Givinostat Combination.Frontiers in pharmacology · 2022Article
- Analysis of multiple gene co-expression networks to discover interactions favoring CFTR biogenesis and ΔF508-CFTR rescue.BMC medical genomics · 2021Article
- Phosphorylation of the Chaperone-Like HspB5 Rescues Trafficking and Function of F508del-CFTR.International journal of molecular sciences · 2020Article
- Article
- IRE1α kinase-mediated unconventional protein secretion rescues misfolded CFTR and pendrin.Science advances · 2020Article
- Human pantothenate kinase 4 is a pseudo-pantothenate kinase.Protein science : a publication of the Protein Society · 2019Article
- Structure-guided combination therapy to potently improve the function of mutant CFTRs.Nature medicine · 2018Article
- Pharmacoperones as Novel Therapeutics for Diverse Protein Conformational Diseases.Physiological reviews · 2018Review
- Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase.Developmental cell · 2018Article
- High-Content Surface and Total Expression siRNA Kinase Library Screen with VX-809 Treatment Reveals Kinase Targets that Enhance F508del-CFTR Rescue.Molecular pharmaceutics · 2018Article
- Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.Frontiers in pharmacology · 2017Review
- Ribosomal Stalk Protein Silencing Partially Corrects the ΔF508-CFTR Functional Expression Defect.PLoS biology · 2016Article
- Article
- Hallmarks of therapeutic management of the cystic fibrosis functional landscape.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the Cystic fibrosis transmembrane conductance regulator (CFTR). ΔF508-CFTR, the most common disease-causing CF mutant, exhibits folding and trafficking defects and is retained in the endoplasmic reticulum, where it is targeted for proteasomal degradation. To identify signaling pathways involved in ΔF508-CFTR rescue, we screened a library of endoribonuclease-prepared short interfering RNAs (esiRNAs) that target ∼750 different kinases and associated signaling proteins. We identified 20 novel suppressors of ΔF508-CFTR maturation, including the FGFR1. These were subsequently validated by measuring channel activity by the YFP halide-sensitive assay following shRNA-mediated knockdown, immunoblotting for the mature (band C) ΔF508-CFTR and measuring the amount of surface ΔF508-CFTR by ELISA. The role of FGFR signaling on ΔF508-CFTR trafficking was further elucidated by knocking down FGFRs and their downstream signaling proteins: Erk1/2, Akt, PLCγ-1, and FRS2. Interestingly, inhibition of FGFR1 with SU5402 administered to intestinal organoids (mini-guts) generated from the ileum of ΔF508-CFTR homozygous mice resulted in a robust ΔF508-CFTR rescue. Moreover, combination of SU5402 and VX-809 treatments in cells led to an additive enhancement of ΔF508-CFTR rescue, suggesting these compounds operate by different mechanisms. Chaperone array analysis on human bronchial epithelial cells harvested from ΔF508/ΔF508-CFTR transplant patients treated with SU5402 identified altered expression of several chaperones, an effect validated by their overexpression or knockdown experiments. We propose that FGFR signaling regulates specific chaperones that control ΔF508-CFTR maturation, and suggest that FGFRs may serve as important targets for therapeutic intervention for the treatment of CF.
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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.