CK2

CK2 (casein kinase 2) is a conserved, constitutively active serine/threonine kinase that regulates protein stability, protein-protein interactions, and subcellular localization through phosphorylation^[1]. Mechanistically, CK2 connects developmental and cancer biology through Wnt and NF-κB signaling, and loss of catalytic subunits can be lethal in development^[1]. In cancer contexts, CK2 supports malignant phenotypes by influencing apoptosis, DNA damage responses, and cell-cycle regulation^[2]. Compared with related catalytic isoforms, CK2α′ shows distinct disease relevance because TNF-induced CK2α′ phosphorylates BRMS1 at Ser30, promoting 14-3-3ε-mediated nuclear export and proteasomal degradation in NSCLC metastasis models^[3]. In orthotopic lung cancer metastasis models, BRMS1 Ser30 mutation or CX-4945 reduced CK2α′-induced migration, invasion, and metastasis^[3]. CK2 also regulates immune differentiation because CX-4945 inhibited Th17 differentiation, promoted Foxp3⁺ Treg generation, and suppressed PI3K/Akt/mTOR activation and STAT3 phosphorylation^[4]. For experimental applications, CK2 inhibitors such as CX-4945 provide tools to test CK2-dependent signaling, tumor invasion, metastasis, and immune-cell polarization^[3][4][5].