Deciphering the role of protein kinase CK2 in the maturation/stability of F508del-CFTR

Publication date: Available online 15 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Claudio D'Amore, Christian Borgo, Valentina Bosello-Travain, Jordi Vilardell, Valentina Salizzato, Lorenzo A. Pinna, Andrea Venerando, Mauro SalviAbstractF508del-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, disclosin...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research