Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

Am J Physiol Lung Cell Mol Physiol. 2016 Oct 1;311(4):L719-L733. doi: 10.1152/ajplung.00431.2015. Epub 2016 Jul 29.

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.

Keywords: cystic fibrosis; glycosylation; palmitoylation; phosphorylation; protein trafficking; ubiquitination.

Publication types

  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Glycosylation
  • Humans
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Protein Stability
  • Protein Transport

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator