Cystic fibrosis transmembrane regulator fragments with the Phe508 deletion exert a dual allosteric control over the master kinase CK2

Cystic fibrosis mostly follows a single Phe(508) deletion in CFTR (cystic fibrosis transmembrane regulator) (CFTR Delta F508), thereby causing premature fragmentation of the nascent protein with concomitant alterations of diverse cellular functions. We show that CK2, the most pleiotropic protein kinase, undergoes allosteric control of its different cellular forms in the presence of short CFTR peptides encompassing the Phe(508) deletion: these CFTR Delta F508 peptides drastically inhibit the isolated catalytic subunit (alpha) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non-catalytic (beta) subunits. Remarkable agreement between in silico docking and Our biochemical data point to different sites for the CFTR Delta F508 peptide binding on isolated CK2 alpha and on CK2 beta assembled into the holoenzyme, suggesting that CK2 targeting may be perturbed in cells expressing CFTR Delta F508; this Could shed light oil some pleiotropic aspects of cystic fibrosis disease.