CFTR fragments with the F508 deletion exert a dual allosteric control over the master kinase CK2.

International audienceCystic Fibrosis (CF) mostly follows a single F508 deletion in CFTR (ΔF508), 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 F508 deletion: these ΔF508 peptides drastically inhibit the isolated catalytic subunit (α) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non catalytic (β) subunits. Remarkable agreement between in silico docking and our biochemical data point to different sites for CFTR-ΔF peptide binding on isolated CK2α and on CK2β assembled into the holoenzyme suggesting that CK2 targeting may be perturbed in cells expressing ΔF508CFTR; this could shed light on some pleiotropic aspects of CF disease