Putting CHIP(s) on the Table: Introducing Nitrosothiols into the Arena of CFTR Modulation

• Published in: American journal of respiratory cell and molecular biology Vol. 61; no. 6; pp. 673 - 675
• Main Authors: Addy, Charlotte, Schock, Bettina C
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-12-2019
• Subjects: Autosomal recessive inheritance; Chloride conductance; Chromosome 7; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Denaturation; Gene deletion; Genetics; Humans; Intestine; Mutation; Pancreas; Phenylalanine; Protein folding; Proteins; S-Nitrosothiols; Secretions; Sodium conductance; Therapeutic applications
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2019-0045ED

Cystic fibrosis (CF) is an autosomal-recessive, genetically based, life-limiting disease characterized by viscid secretions in multiple organ systems. The cystic fibrosis transmembrane conductance regulator gene (CFTR), on chromosome 7, codes for a cAMP-regulated chloride channel on multiple epithelial surfaces, including the airways, pancreas, and intestine. Mutations can affect the CFTR protein at any point, including during formation, maturation, intracellular trafficking, surface function, and denaturation. Over 2,000 mutations have been described, with a phenylalanine deletion resulting in misfolded protein and accelerated degradation being the most common disease-causing mutation. Defective CFTR function impairs chloride conductance, with associated defective sodium transport across epithelial surfaces resulting in the generation of viscid secretions that are the hallmark of CF. Here, Addy and Schock discuss a novel alternative to current approaches for modulating CFTR, described by Zaman et al in this issue (pp. 765-775). This study highlights a novel therapeutic target, nitrosylation of CHIP, with the potential to provide an innovative means of modulating CFTR. Selective modification of the QC machinery remains an attractive approach.