The researchers performed in vitro and in cells studies to demonstrate how CK2 can affect F508del stability using transfections, specific CK2 kinase inhibitors and CK2 knockout cells.
They have demonstrated that CK2 inhibition may represent an important tool to reduce the expression of HSP27, a chaperone that specifically recognizes F508del leading to its ubiquitylation and degradation. Moreover, the detailed mechanisms by which HSP27 expression is regulated by CK2 has been elucidated. However, the direct correlation between CK2-HSP27-CFTR-F508del is still lacking and is under study. The extension project FFC#12/2017 aims at providing the rationale for the use of CK2 inhibitors in combinatory therapies with correctors or proteostasis regulators for the rescue and stabilization of F508delCFTR at the plasma membrane.