Kopito R R
Department of Biological Sciences, Stanford University, Stanford, California, USA.
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.
囊性纤维化跨膜传导调节因子（CFTR）的生物合成与降解。《生理学评论》79卷，增刊：S167 - S173，1999年。——许多导致囊性纤维化的囊性纤维化跨膜传导调节因子（CFTR）基因突变会干扰内质网中新生CFTR分子的折叠和生物合成过程。包括常见等位基因DeltaF508在内的胞质核苷酸结合结构域中的突变，降低了CFTR折叠的效率，降低了其与分子伴侣解离的概率，并在很大程度上阻止了其通过分泌途径成熟至质膜。这些突变的CFTR分子通过需要多聚泛素化共价修饰的过程被胞质蛋白酶体迅速降解。温度和化学伴侣对突变CFTR分子细胞内加工的影响表明，旨在提高该蛋白体内折叠产量的策略最终可能会导致开发出治疗囊性纤维化的新疗法。
