Biosynthesis and degradation of CFTR.
Biosynthesis and degradation of CFTR.
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CFTR 的生物合成和降解。
DOI：
10.1152/physrev.1999.79.1.s167
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
Kopito,RR
中科院分区：
文献类型：
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作者：
Kopito,RR
Kopito，罗恩R. CFTR的生物合成和降解。生理学修订版79，增刊：S167-S173，1999年。- 囊性纤维化跨膜传导调节因子（CFTR）基因中的许多突变导致囊性纤维化，干扰内质网中新生CFTR分子的折叠和生物合成过程。细胞质核苷酸结合结构域中的突变，包括常见等位基因ΔF508，降低了CFTR折叠的效率，降低了其从分子伴侣解离的可能性，并在很大程度上阻止了其通过分泌途径成熟到质膜。这些突变的CFTR分子被细胞质蛋白酶体通过需要通过多泛素化进行共价修饰的过程快速降解。温度和化学伴侣对突变CFTR分子的细胞内加工的影响表明，旨在增加这种蛋白质在体内的折叠产量的策略可能最终导致囊性纤维化的新疗法的发展。
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.