title: Emergent properties of proteostasis in managing cystic fibrosis.
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.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. webalch@scripps.edu
authors.forename: William E
authors.initials: WE
authors.lastname: Balch
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Roth
authors.forename: Darren M
authors.initials: DM
authors.lastname: Hutt
mesh_terms: D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D019468:Disease Management; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology; D057165:Proteostasis Deficiencies / Q000378:metabolism*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator