Pranke Iwona M, Sermet-Gaudelus Isabelle
INSERM U1151 - Faculté de Médecine, Université Paris Descartes, 14 Rue Maria Helena Vieira Da Silva, 75014 Paris, France.
INSERM U1151 - Faculté de Médecine, Université Paris Descartes, 14 Rue Maria Helena Vieira Da Silva, 75014 Paris, France; Centre de Référence et de Competence en Mucoviscidose, Service de Pneumologie et d'Allergologie Pédiatriques, Hôpital Necker, 149 rue de Sévres, 75015 Paris, France.
Int J Biochem Cell Biol. 2014 Jul;52:26-38. doi: 10.1016/j.biocel.2014.03.020. Epub 2014 Mar 28.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride (Cl(-)) channel. Mutations of its gene lead to the disease of cystis fibrosis (CF) among which the most common is the deletion of phenylalanine at position 508 (Phe508del). CFTR is a multi-domain glycoprotein whose biosynthesis, maturation and functioning as an anion channel involve multi-level post-translational modifications of CFTR molecules and complex folding processes to reach its native, tertiary conformation. Only 20-40% of the nascent chains achieve folded conformation, while the remaining molecules are targeted for degradation by endoplasmic reticulum, lysosomes, or autophagy. A large number of mutations causing CF impair processing of CFTR. Growing knowledge of CFTR biosynthesis has enabled understanding the cellular basis of CF and has brought to light various potential targets for novel, promising therapies.
囊性纤维化跨膜传导调节因子（CFTR）是一种受环磷酸腺苷（cAMP）调节的氯离子（Cl⁻）通道。其基因突变会导致囊性纤维化（CF）疾病，其中最常见的是第508位苯丙氨酸缺失（Phe508del）。CFTR是一种多结构域糖蛋白，其生物合成、成熟以及作为阴离子通道发挥功能涉及CFTR分子的多级翻译后修饰和复杂的折叠过程，以达到其天然的三级构象。只有20% - 40%的新生链能够形成折叠构象，而其余分子则被内质网、溶酶体或自噬作用靶向降解。大量导致CF的突变会损害CFTR的加工过程。对CFTR生物合成的深入了解有助于理解CF的细胞基础，并揭示了各种有前景的新型治疗潜在靶点。
