Related Experiment Video
Updated: Jul 14, 2026
15:12
Purification of the Cystic Fibrosis Transmembrane Conductance Regulator Protein Expressed in Saccharomyces cerevisiae
Published on: May 10, 2014
Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations
M Howard1, R A Frizzell, D M Bedwell
1Department of Physiology, University of Alabama at Birmingham, 35294, USA.
Nature Medicine
|April 1, 1996
Summary
Aminoglycoside antibiotics like G-418 can suppress premature stop mutations in cystic fibrosis (CF) transmembrane conductance regulator (CFTR) genes. This treatment restores CFTR function, offering a potential therapy for CF patients with these specific mutations.
Area of Science:
- Genetics and Molecular Biology
- Pharmacology
- Cell Biology
Background:
- Cystic fibrosis (CF) is a genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene.
- The deltaF508 mutation is the most common, but premature stop mutations also cause severe CF.
- Restoring CFTR protein function is a key therapeutic goal.
Purpose of the Study:
- To investigate the potential of aminoglycoside antibiotics to suppress premature stop mutations in CFTR.
- To determine if G-418 and gentamicin can restore CFTR protein expression and function.
Main Methods:
- Cell culture models with common CF-associated premature stop mutations were treated with low doses of G-418.
- CFTR expression and function were assessed following aminoglycoside treatment.
- The effect of gentamicin on CFTR expression was also evaluated.
Main Results:
- Low-dose G-418 treatment suppressed two common disease-associated stop mutations.
- Aminoglycoside treatment led to the expression of full-length CFTR protein.
- Restored CFTR protein exhibited cyclic AMP-activated chloride channel activity.
Conclusions:
- Aminoglycosides, including G-418 and gentamicin, can promote the expression of full-length CFTR.
- This approach may offer a therapeutic strategy for CF patients with premature stop mutations.
- Further research is warranted to explore aminoglycoside therapy for CF.
Related Concept Videos
02:46Genome Copying Errors
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:24Cystic Fibrosis: Management
Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic sinusitis...
Sinus disease and chronic sinusitis...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:25Inhibitors of Bacterial Protein Synthesis
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...