Journal article
Transcriptomic and Proteostasis Networks of CFTR and the Development of Small Molecule Modulators for the Treatment of Cystic Fibrosis Lung Disease
Genes, Vol.11(5), p.546
05/01/2020
DOI: 10.3390/genes11050546
PMCID: PMC7288469
PMID: 32414011
Abstract
Cystic fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The diversity of mutations and the multiple ways by which the protein is affected present challenges for therapeutic development. The observation that the Phe508del-CFTR mutant protein is temperature sensitive provided proof of principle that mutant CFTR could escape proteosomal degradation and retain partial function. Several specific protein interactors and quality control checkpoints encountered by CFTR during its proteostasis have been investigated for therapeutic purposes, but remain incompletely understood. Furthermore, pharmacological manipulation of many CFTR interactors has not been thoroughly investigated for the rescue of Phe508del-CFTR. However, high-throughput screening technologies helped identify several small molecule modulators that rescue CFTR from proteosomal degradation and restore partial function to the protein. Here, we discuss the current state of CFTR transcriptomic and biogenesis research and small molecule therapy development. We also review recent progress in CFTR proteostasis modulators and discuss how such treatments could complement current FDA-approved small molecules.
Details
- Title: Subtitle
- Transcriptomic and Proteostasis Networks of CFTR and the Development of Small Molecule Modulators for the Treatment of Cystic Fibrosis Lung Disease
- Creators
- Matthew D. Strub - University of IowaPaul B. McCray - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Genes, Vol.11(5), p.546
- DOI
- 10.3390/genes11050546
- PMID
- 32414011
- PMCID
- PMC7288469
- NLM abbreviation
- Genes (Basel)
- ISSN
- 2073-4425
- eISSN
- 2073-4425
- Publisher
- Mdpi
- Number of pages
- 27
- Grant note
- T32GM008629 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Cystic Fibrosis Foundation; Italian Cystic Fibrosis Research Foundation DK54759 / University of Iowa Center for Gene Therapy UG3 HL-147366; P01 HL51670; P01 HL091842 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Roy J. Carver Chair in Pulmonary Research
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984297330702771
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