Emergent properties of proteostasis in managing cystic fibrosis

Cold Spring Harb Perspect Biol. 2011 Feb 1;3(2):a004499. doi: 10.1101/cshperspect.a004499.

Abstract

Cystic fibrosis (CF) is a consequence of defective recognition of the multimembrane spanning protein cystic fibrosis conductance transmembrane regulator (CFTR) by the protein homeostasis or proteostasis network (PN) (Hutt and Balch (2010). Like many variant proteins triggering misfolding diseases, mutant CFTR has a complex folding and membrane trafficking itinerary that is managed by the PN to maintain proteome balance and this balance is disrupted in human disease. The biological pathways dictating the folding and function of CFTR in health and disease are being studied by numerous investigators, providing a unique opportunity to begin to understand and therapeutically address the role of the PN in disease onset, and its progression during aging. We discuss the general concept that therapeutic management of the emergent properties of the PN to control the energetics of CFTR folding biology may provide significant clinical benefit.

Publication types

  • Review

MeSH terms

  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Disease Management
  • Drug Discovery / methods*
  • Humans
  • Models, Biological
  • Mutation / genetics
  • Protein Folding*
  • Protein Transport / physiology
  • Proteostasis Deficiencies / metabolism*

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator