Biosynthesis and degradation of CFTR

RR Kopito - Physiological reviews, 1999 - journals.physiology.org
Physiological reviews, 1999journals.physiology.org
Kopito, Ron R. 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 ΔF508, decrease the
efficiency of CFTR folding, reduce the probability of its dissociation from molecular …
Kopito, Ron R. 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 ΔF508, 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.
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