The ones with the most well-defined role of CK2 are shown in Fig. Its intervention that might cause dysregulation relevant for human diseases has been dissected in several signaling pathways. Among the many CK2 substrates, components of diverse signaling pathways are present, implying that CK2 controls important cellular processes, frequently producing abnormal responses and contributing to pathological phenotypes. It is instead already present and ready to play its “horizontal” function on pathways that are otherwise activated. 5, 6 In fact, being constitutively active, it does not respond to a figuratively “vertical” stimulus coming from outside the cell. In signal transduction, CK2 is defined as a “lateral player”. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.ĬK2 functions and involvement in signal transduction On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). Other well-known functions of CK2 are in human infections in particular, several viruses exploit host cell CK2 for their life cycle. Its best documented role is in cancer, where it regulates practically all malignant hallmarks.
CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases.
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