Biosynthesis and degradation of CFTR

Physiol Rev. 1999 Jan;79(1 Suppl):S167-73. doi: 10.1152/physrev.1999.79.1.S167.


Biosynthesis and Degradation of CFTR. Physiol. Rev. 79, Suppl.: S167-S173, 1999. - Many of the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause cystic fibrosis interfere with the folding and biosynthetic processing of nascent CFTR molecules in the endoplasmic reticulum. Mutations in the cytoplasmic nucleotide binding domains, including the common allele DeltaF508, decrease the efficiency of CFTR folding, reduce the probability of its dissociation from molecular chaperones, and largely prevent its maturation through the secretory pathway to the plasma membrane. These mutant CFTR molecules are rapidly degraded by cytoplasmic proteasomes by a process that requires covalent modification by multiubiquitination. The effects of temperature and chemical chaperones on the intracellular processing of mutant CFTR molecules suggest that strategies aimed at increasing the folding yield of this protein in vivo may eventually lead to the development of novel therapies for cystic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis / therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator / biosynthesis*
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Endopeptidases / metabolism
  • Endoplasmic Reticulum, Rough / metabolism
  • Humans
  • Molecular Chaperones / metabolism
  • Mutation
  • Protein Folding
  • Protein Precursors / metabolism
  • Ubiquitins / metabolism


  • CFTR protein, human
  • Molecular Chaperones
  • Protein Precursors
  • Ubiquitins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Endopeptidases