Protein kinase CK2: a potential therapeutic target for diverse human diseases

Abstract

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. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. 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). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. 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. 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.

Targeting CK2 in cancer: a valuable strategy or a waste of time?

“…CK2 is a protein kinase implicated in many human diseases [ 1 ]. Recently, it has been found relevant also in the viral infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its exploitation as a COVID-19 target is under investigation [ 2 , 3 ].…”

Tyrosine 136 phosphorylation of α-synuclein aggregates in the Lewy body dementia brain: involvement of serine 129 phosphorylation by casein kinase 2

“…Unexpectedly, phosphorylation of Y136 in αSyn aggregates was significantly increased by TBB in cultured cells, suggesting that CK2 plays an inhibitory role against Y136 phosphorylation in cells. As CK2 phosphorylates hundreds of physiological substrates to control various cellular processes [ 5 ], its in vitro and in vivo functions may not be consistent. CK2 has been reported to phosphorylate threonine residues of Src family tyrosine kinases, thereby resulting in reduction of their activities in vitro [ 38 ].…”

The Immune Regulatory Role of Protein Kinase CK2 and Its Implications for Treatment of Cancer

“…CK2 is constitutively active and can phosphorylate either serine/threonine or tyrosine residues, and the number of its target substrates are more than five hundred [ 1 , 11 ]. The phosphorylation function of CK2 occurs via recognizing its consensus sequence (S-X-X-E/D/Yp/Sp) [ 13 , 14 ].…”

“…The notion that CK2 is implicated in the pathogenesis of a plethora of diseases is well-established [ 1 ]. First discovered by George Burnett and Eugene P. Kennedy more than 6 decades ago [ 2 ], the field of CK2 biology has exploded with studies investigating phosphorylation targets of CK2, the cellular biology of CK2, and the important roles of CK2 in normal biological processes and disease pathogenesis.…”