Casein kinase 2

Protein
Casein kinase 2 (CK2/CSNK2) is a serine/threonine selective protein kinase that has been implicated in cell cycle control, DNA repair, regulation of the circadian rhythm, and other cellular processes. De regulation of CK2 has been linked to tumorigenesis as a potential protection mechanism for mutated cells. Proper CK2 function is necessary for survival of cells as no knockout models have been successfully generated.

CK2 typically appears as a tetramer of two α subunits; α being 42 kDa and α’ being 38 kDa, and two β subunits, each weighing in at 28 kDa. and therefore within the tetramer will have two β subunits. The catalytic α domains appear as an α or α’ variant and can either be formed in a homodimer (α & α, or α’ & α’) formation or heterodimer formation (α & α’). A functional difference between α and α’ has been found but the exact nature of differences isn't fully understood yet. An example is that Caspase 3 is preferentially phosphorylated by α’ based tetramers over α based tetramers.

Although the targets of CK2 are predominantly nucleus based the protein itself is localized to both the nucleus and cytoplasm. A Pertussis toxin sensitive G protein and Dishevelled appear to be an intermediary between Wnt mediated activation of the Frizzled receptor and activation of CK2. Further studies need to be done on the regulation of this protein due to the complexity of CK2 function and localization. Phosphorylation of CK2α T344 has been shown to inhibit its proteasomal degradation and support binding to Pin1. O GlcNAcylation at S347 antagonizes this phosphorylation and accelerates CK2α degradation. O GlcNAcylation of CK2α has also been shown to alter the phosphoproteome, notably including many chromatin regulators such as HDAC1, HDAC2, and HCFC1.

Among the array of substrates that can be altered by CK2 many of them have been found in increased prevalence in cancers of the breast, lung, colon, and prostate. Senhwa Biosciences and the US National Institutes of Health have announced that they will evaluate the efficacy of silmitasertib in treating COVID 19 infections.