ArticleMolecular & cellular proteomics : MCP2009
High-content functional screen to identify proteins that correct F508del-CFTR function.
Article in Molecular & cellular proteomics : MCP, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Integrative genomic meta-analysis reveals novel molecular insights into cystic fibrosis and ΔF508-CFTR rescue.Scientific reports · 2020Pooled it
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Accurate rare variant phasing of whole-genome and whole-exome sequencing data in the UK Biobank.Nature genetics · 2023Article
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Analysis of multiple gene co-expression networks to discover interactions favoring CFTR biogenesis and ΔF508-CFTR rescue.BMC medical genomics · 2021Article
- Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking.Scientific reports · 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
- Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia.NPJ genomic medicine · 2017Article
- In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.PloS one · 2017Article
- Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.Frontiers in pharmacology · 2017Review
- Article
- Hallmarks of therapeutic management of the cystic fibrosis functional landscape.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2015Review
- Characterization of Zinc Influx Transporters (ZIPs) in Pancreatic β Cells: ROLES IN REGULATING CYTOSOLIC ZINC HOMEOSTASIS AND INSULIN SECRETION.The Journal of biological chemistry · 2015Article
- Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis.PLoS genetics · 2015Article
- RNA Interference Screen to Identify Kinases That Suppress Rescue of ΔF508-CFTR.Molecular & cellular proteomics : MCP · 2015Article
- ESCRT regulates surface expression of the Kir2.1 potassium channel.Molecular biology of the cell · 2014Article
- The contribution of systematic approaches to characterizing the proteins and functions of the endoplasmic reticulum.Cold Spring Harbor perspectives in biology · 2013Review
- Use of kinase inhibitors to correct ΔF508-CFTR function.Molecular & cellular proteomics : MCP · 2012Article
- Disruption of cytokeratin-8 interaction with F508del-CFTR corrects its functional defect.Human molecular genetics · 2012Article
- TFG-1 function in protein secretion and oncogenesis.Nature cell biology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic Fibrosis is caused by mutations in CFTR, with a deletion of a phenylalanine at position 508 (F508del-CFTR) representing the most common mutation. The F508del-CFTR protein exhibits a trafficking defect and is retained in the endoplasmic reticulum. Here we describe the development of a high-content screen based on a functional assay to identify proteins that correct the F508del-CFTR defect. Using a HEK293 MSR GripTite cell line that stably expresses F508del-CFTR, we individually co-expressed approximately 450 unique proteins fused to the Cl(-)-sensitive YFP(H148Q/I152L) mutant. We then tested correction of F508del-CFTR function by the CI(-)/l(-) exchange method following stimulation with forskolin/IBMX/genistein, using quantitative recordings in multiple individual cells with a high-content (high-throughput) Cellomics KSR imaging system. Using this approach, we identified several known and novel proteins that corrected F508del-CFTR function, including STAT1, Endothelin 1, HspA4, SAPK substrate protein 1, AP2M1, LGALS3/galectin-3, Trk-fused gene, Caveolin 2, PAP/REG3alpha, and others. The ability of these correctors to rescue F508del-CFTR trafficking was then validated by demonstrating their enhancement of maturation (appearance of band C) and by cell surface expression of F508del-CFTR bearing HA tag at the ectodomain using confocal microscopy and flow cytometry. These data demonstrate the utility of high-content analyses for identifying proteins that correct mutant CFTR and discover new proteins that stimulate this correction. This assay can also be utilized for RNAi screens to identify inhibitory proteins that block correction of F508del-CFTR, small molecule, and peptide screens.
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