Casein kinase II subunit alpha' (CSNK2A2) (CSNK2A2)

Casein kinase II subunit alpha' (CSNK2A2) is a catalytic subunit of the pleiotropic and constitutively active serine/threonine protein kinase complex, Casein Kinase 2 (CK2) [UniProt: P19784]. While it shares significant structural homology with the CK2 alpha isoform, CK2 alpha' is encoded by a separate gene and possesses distinct physiological roles, particularly in male germ cell development and specific oncogenic contexts [PubMed: 15561715]. The enzyme phosphorylates a vast array of substrates involved in DNA damage repair, cell cycle control, and the regulation of apoptosis, often acting as a pro-survival factor [NCBI Gene: 1459]. In many cancers, CK2 alpha' is upregulated, driving tumor progression by activating the PI3K/Akt and NF-kappaB pathways while inhibiting tumor suppressors like p53 [PubMed: 25151357]. Pharmacological inhibition of CK2 alpha' is a burgeoning area of research, with ATP-competitive inhibitors such as Silmitasertib (CX-4945) demonstrating efficacy in clinical trials by inducing apoptosis in malignant cells [ClinicalTrials.gov: NCT02128282]. However, the ubiquitous nature and essential functions of CK2 present challenges in achieving selective inhibition without systemic toxicity [PubMed: 29107105].

Other names

CK2 alpha primeCK2A2Casein kinase 2 alpha 2CSNK2A1LCKII alpha primeCasein kinase II alpha'

ATP-competitive inhibition of the catalytic activity of the CK2 alpha' subunit, which prevents the phosphorylation of downstream substrates such as Akt, p53, and various transcription factors, thereby inhibiting pro-survival signaling and inducing apoptosis in cancer cells [PubMed: 21148473, PubMed: 25151357].