While activation of NF-κB by many stimuli depends on the phosphorylation of IκBs at N-terminal sites by the IKK complex, the mechanism of NF-κB activation by ultraviolet (UV) radiation involves the IKK-independent phosphorylation of IκBα at a cluster of C-terminal sites that are recognized by casein kinase II (CKII). CKII activity toward IκBα depends on p38 mitogen-activated protein kinase (MAPK) activation. CKII’s role as a key survival signal that activates NF-κB and protects tumor cells from apoptosis suggests that CKII may be an attractive target for the treatment of diverse cancers. Apigenin, a plant flavonoid, and emodin, a plant anthraquinone, are competitive inhibitors of CKII that directly interact with the nucleotide-binding sites of CKII [48].
