Casein kinase 1 isoform alpha (CK1α)

Casein kinase 1 isoform alpha (CK1α), encoded by the CSNK1A1 gene, is a ubiquitous serine/threonine-selective protein kinase that serves as a critical regulator of diverse cellular signaling pathways, most notably the Wnt/beta-catenin and p53 pathways [2, 11]. As a key component of the beta-catenin destruction complex, CK1α phosphorylates beta-catenin at Ser45, priming it for subsequent degradation and thereby acting as a negative regulator of Wnt signaling [11, 16]. In the context of the p53 pathway, CK1α regulates p53 stability and activity by interacting with and phosphorylating its negative regulators, MDM2 and MDMX [11, 18]. The target has gained significant therapeutic interest in hematology, particularly in myelodysplastic syndrome (MDS) with deletion of chromosome 5q, where the CSNK1A1 gene is located; haploinsufficiency of CK1α in these cells creates a therapeutic vulnerability that can be exploited by molecular glue degraders like lenalidomide [8, 11]. Beyond MDS, CK1α is implicated in acute myeloid leukemia (AML), colorectal cancer, and neurodegenerative diseases such as Alzheimer's, where it contributes to tau protein phosphorylation [9, 12, 20]. Pharmacological strategies targeting CK1α include ATP-competitive small molecule inhibitors and targeted protein degraders, which aim to induce p53-mediated apoptosis in malignant cells [1, 14, 18].

Other names

CSNK1A1CK1aCasein kinase I alphaCKIaCKIalphaCK1-alphaHCKII

Targeted protein degradation via E3 ligase recruitment (molecular glue) and ATP-competitive inhibition of kinase activity [11, 14, 18].