Emergent Properties of Proteostasis in Managing Cystic Fibrosis |
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| Authors: | William E Balch Daniela M Roth Darren M Hutt |
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| Institution: | 1Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037;2The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037;3Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037;4The Institute for Childhood and Neglected Diseases, The Scripps Research Institute, La Jolla, California 92037 |
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| 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. |
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