F508del-CFTR, the most common mutation in cystic fibrosis (CF) patients, impairs CFTR trafficking to plasma membrane leading to its premature proteasomal degradation. Several post-translational modifications have been identified on CFTR with multiple roles in stability, localization and channel function, and the possibility to control the enzymes responsible of these modifications has been long considered a potential therapeutic strategy. Protein kinase CK2 has been previously suggested as an important player in regulating CFTR functions and it has been proposed as a pharmacological target in a combinatory therapy to treat CF patients. However, the real implication of CK2 in F508del-CFTR proteostasis, and in particular the hypothesis that its inhibition could be important in CF therapies, is still elusive. Here, by using immortalized cell lines, primary human cells, and knockout cell lines deprived of CK2 subunits, we do not disclose any direct correlation between F508del-CFTR proteostasis and CK2 expression/activity. Rather, our data indicate that the CK2α' catalytic subunit should be preserved rather than inhibited for F508del rescue by the correctors of class-1, such as VX-809, disclosing new important features in CF therapeutic approaches.

中文翻译：

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破译蛋白激酶CK2在F508del-CFTR的成熟/稳定性中的作用。

F508del-CFTR是囊性纤维化（CF）患者中最常见的突变，它会损害CFTR转运至质膜，导致其蛋白酶体过早降解。已经在CFTR上鉴定了几种翻译后修饰，它们在稳定性，定位和通道功能上具有多种作用，并且控制这些修饰酶的可能性一直以来被认为是一种潜在的治疗策略。先前已经提出蛋白激酶CK2在调节CFTR功能中起重要作用，并且已被提议作为组合疗法治疗CF患者的药理学靶标。然而，CK2在F508del-CFTR蛋白稳态中的真正含义，尤其是其抑制在CF疗法中可能很重要的假设，仍然难以捉摸。在这里，通过使用永生的细胞系，原代人细胞和缺少CK2亚基的基因敲除细胞系，我们没有揭示F508del-CFTR蛋白变形与CK2表达/活性之间的任何直接关系。相反，我们的数据表明，应该保留CK2α'催化亚基，而不是通过揭示CF治疗方法新的重要特征的1类校正剂（例如VX-809）来抑制F508del的拯救。