Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-4684-5934-0_39 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells.
Biochim Biophys Acta
May 2015
NSERM U1078, Université Bretagne Occidentale, 22 Avenue Camille Desmoulins, 29200 Brest, France. Electronic address:
Cystic Fibrosis (CF) disease is caused by mutations in the CFTR gene (CF transmembrane conductance regulator). F508 deletion is the most represented mutation, and F508del-CFTR is absent of plasma membrane and accumulates into the endoplasmic reticulum (ER) compartment. Using specific Ca2+ genetics cameleon probes, we showed in the human bronchial CF epithelial cell line CFBE that ER Ca2+ concentration was strongly increased compared to non-CF (16HBE) cells, and normalized by the F508del-CFTR corrector agent, VX-809.
View Article and Find Full Text PDFCorrection of F508del-CFTR trafficking by the sponge alkaloid latonduine is modulated by interaction with PARP.
Chem Biol
October 2012
Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada.
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause CF. The most common mutation, F508 deletion, causes CFTR misfolding and endoplasmic reticulum retention, preventing it from trafficking to the cell surface. One approach to CF treatment is to identify compounds that correct the trafficking defect.
View Article and Find Full Text PDFSmall molecule correctors of F508del-CFTR discovered by structure-based virtual screening.
J Comput Aided Mol Des
December 2010
EPIX Pharmaceuticals Ltd., 3 Hayetzira Street, Ramat Gan, Israel.
Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability.
View Article and Find Full Text PDFRegulatory insertion removal restores maturation, stability and function of DeltaF508 CFTR.
J Mol Biol
August 2010
Department of Biomedical Engineering, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
The cystic fibrosis transmembrane conductance regulator (CFTR) epithelial anion channel is a large multidomain membrane protein that matures inefficiently during biosynthesis. Its assembly is further perturbed by the deletion of F508 from the first nucleotide-binding domain (NBD1) responsible for most cystic fibrosis. The mutant polypeptide is recognized by cellular quality control systems and is proteolyzed.
View Article and Find Full Text PDFModulation of protein kinase CK2 activity by fragments of CFTR encompassing F508 may reflect functional links with cystic fibrosis pathogenesis.
Biochemistry
July 2008
Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, viale G. Colombo 3, 35131 Padova, Italy.
Deletion of F508 in the first nucleotide binding domain (NBD1) of cystic fibrosis transmembrane conductance regulator protein (CFTR) is the commonest cause of cystic fibrosis (CF). Functional interactions between CFTR and CK2, a highly pleiotropic protein kinase, have been recently described which are perturbed by the F508 deletion. Here we show that both NBD1 wild type and NBD1 DeltaF508 are phosphorylated in vitro by CK2 catalytic alpha-subunit but not by CK2 holoenzyme unless polylysine is added.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!