title: Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications.
abstract: Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR PTMs may suggest novel treatment strategies for CF and perhaps other protein conformational diseases. This review provides a comprehensive summary of co- and posttranslational CFTR modifications and their significance with regard to protein biogenesis.
authors.affiliation: Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: McClure
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia esorscher@emory.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D021381:Protein Transport
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: cystic fibrosis; glycosylation; palmitoylation; phosphorylation; protein trafficking; ubiquitination