PROTEIN KINASE CK2 IN HUMAN DISEASES: TOO MUCH OR TOO LITTLE?

CK2 is a protein kinase composed by two catalytic subunits α or α′, that can be active also as monomers, and two regulatory subunits β. CK2 is constitutively active and, by phosphorylating hundreds of substrates, is involved in different signaling pathways, as the PI3K/Akt, the IKK/NFκB, the JAK2/STAT3 and the Wnt/β-catenin pathways. CK2 is also implicated in several human diseases; among them, its role in cancer is the most widely studied, but its pathological functions have been also reported in diabetes, obesity, atherosclerosis, cardiovascular diseases, neurologic disorders, and viral infections. The main aim of this work was the investigation of the role of CK2 in four non-related human diseases, namely Friedrich’s ataxia (FRDA), chronic myeloid leukemia (CML), Poirier-Bienvenu Neurodevelopmental Syndrome (POBINDS) and coronavirus disease 2019 (COVID-19). In summary, this thesis adds evidence to the concept that CK2 is a valuable target for diverse human diseases. Moreover, in addition to the historical view of this enzyme as a “too much” thing, with a pathological role which requires inhibition, here we highlight that also the “too low” condition exists for CK2 as disease-driving molecule. For the physiological functionality of CK2, a balance, the “right level”, is necessary, that, when lost, could require either inhibition or activation.