Protein kinase CK2 holoenzyme (CK2)

Protein kinase CK2 (formerly Casein kinase II) is a highly conserved, ubiquitously expressed serine/threonine protein kinase that typically functions as a heterotetrameric holoenzyme composed of two catalytic subunits (alpha and/or alpha-prime) and two regulatory beta subunits [1]. Unlike most protein kinases, CK2 is constitutively active and does not require specific phosphorylation or second messengers for its activity, allowing it to phosphorylate hundreds of substrates involved in signal transduction, transcription, and DNA repair [2]. In various cancers, CK2 is frequently overexpressed, where it acts as a potent anti-apoptotic and pro-survival factor, making it an attractive target for therapeutic intervention [3]. Small-molecule inhibitors such as Silmitasertib (CX-4945) have been developed to competitively inhibit the ATP-binding site of the catalytic subunits and are currently being evaluated in clinical trials for both solid tumors and hematologic malignancies [4]. Beyond oncology, CK2 is also investigated for its roles in viral infections and neurodegenerative diseases, though its essential role in normal cellular homeostasis presents challenges for achieving a wide therapeutic window [5].

Other names

Casein kinase IICKIICSNK2Casein kinase 2Phosvitin kinase

ATP-competitive inhibition of the catalytic subunits (alpha and alpha-prime) or disruption of the interaction between the catalytic and regulatory (beta) subunits [3, 4].