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Deciphering the role of protein kinase CK2 in the maturation/stability of F508del-CFTR
- Publication Year :
- 2020
- Publisher :
- Elsevier B.V., 2020.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Protein subunit
CK2
Cystic Fibrosis Transmembrane Conductance Regulator
medicine.disease_cause
Cystic fibrosis
Cell Line
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Casein Kinase II
Molecular Biology
chemistry.chemical_classification
Mutation
F508del-CFTR correction
medicine.disease
Cell biology
VX-809
Protein Subunits
030104 developmental biology
Enzyme
Proteostasis
chemistry
Cell culture
030220 oncology & carcinogenesis
Molecular Medicine
Immortalised cell line
Function (biology)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....5755bc4beddb0aad620dcac35bcf1220