Casein kinase 2 catalytic subunit alpha and alpha prime (CK2α and CK2α′)

Casein kinase 2 (CK2) is a constitutively active, ubiquitously expressed serine/threonine protein kinase that plays a fundamental role in regulating cell growth, proliferation, and survival [1.3.1, 1.4.4]. It typically functions as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2α and/or CK2α′) and two regulatory β subunits, though the catalytic subunits can also function independently [1.4.1, 1.6.1]. CK2 is involved in a vast array of signaling pathways, including PI3K/Akt, Wnt/β-catenin, and NF-κB, and it phosphorylates hundreds of substrates involved in DNA repair, transcription, and the cell cycle [1.2.2, 1.6.2]. In many human cancers, CK2 is overexpressed or hyperactivated, leading to a state of "non-oncogene addiction" where tumor cells rely on its activity to suppress apoptosis and maintain a malignant phenotype [1.1.2, 1.3.5]. Beyond oncology, CK2 is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's, where it contributes to the aggregation of pathological proteins, as well as in viral infections and inflammatory conditions [1.2.1, 1.4.2]. Therapeutic targeting of the catalytic subunits, primarily through ATP-competitive small molecules like silmitasertib (CX-4945), aims to induce apoptosis in cancer cells and sensitize them to other treatments, though its pleiotropic nature presents challenges for achieving high selectivity and minimizing systemic toxicity [1.2.2, 1.3.1].

Other names

CSNK2A1CSNK2A2CK II alphaCK II alpha primeCK2A1CK2A2Casein kinase 2 alphaCasein kinase 2 alpha prime

ATP-competitive inhibition of the catalytic subunits (CK2α and CK2α′), preventing the phosphorylation of downstream substrates in survival and proliferation pathways [1.3.1, 1.3.2].