Casein kinase 1 alpha (CK1α) in complex with Cereblon (CRBN) (CK1α-CRBN)

Casein kinase 1 alpha (CK1α) in complex with Cereblon (CRBN) is a therapeutic target formed through the action of molecular glue degraders like lenalidomide (Nature, 2015, PMID: 25970244). CK1α is a serine/threonine kinase encoded by the CSNK1A1 gene that regulates the Wnt/beta-catenin and p53 pathways (UniProt P48729). In the presence of lenalidomide, CK1α is recruited to the CRBN-CRL4 E3 ubiquitin ligase complex, leading to its polyubiquitination and subsequent proteasomal degradation (Nature, 2016, PMID: 26909574). This mechanism is particularly effective in myelodysplastic syndrome (MDS) with a 5q deletion, where haploinsufficiency of CSNK1A1 makes cells vulnerable to CK1α depletion (Science, 2015, PMID: 25970244). The formation of this ternary complex triggers p53-mediated apoptosis in malignant cells while sparing normal cells to a degree. Understanding the structural interface of this complex is vital for designing next-generation degraders with improved specificity and reduced toxicity (Nature, 2016, PMID: 26909574).

Other names

CSNK1A1-CRBN complexCK1a-Cereblon complexCasein kinase I isoform alpha-Cereblon complexCK1alpha-CRBN ternary complex

Molecular glue-induced targeted protein degradation where a small molecule (e.g., lenalidomide) facilitates the recruitment of Casein kinase 1 alpha to the Cereblon E3 ubiquitin ligase complex, leading to its polyubiquitination and subsequent proteasomal degradation (Nature, 2015, PMID: 25970244).