Cyclin-dependent kinase regulatory subunit 1 (CKS1B) (CKS1B)

Cyclin-dependent kinase regulatory subunit 1 (CKS1B) is a highly conserved adaptor protein that functions as an essential component of the SCF-Skp2 E3 ubiquitin ligase complex (UniProt P61073). It specifically mediates the recruitment and subsequent polyubiquitination of the cyclin-dependent kinase inhibitor p27Kip1, leading to its proteasomal degradation and facilitating the G1 to S phase transition of the cell cycle (PubMed: 15175126). In many human cancers, including multiple myeloma, breast cancer, and hepatocellular carcinoma, CKS1B is frequently overexpressed or amplified, which leads to abnormally low levels of p27Kip1 and accelerated cell proliferation (PubMed: 25605873). Consequently, CKS1B is considered a significant oncogenic driver and a valuable prognostic biomarker for aggressive disease (NCBI Gene ID: 1163). Therapeutic strategies targeting CKS1B primarily involve the development of small-molecule inhibitors designed to disrupt the Skp2-Cks1 protein-protein interaction (PubMed: 22438593). By preventing the degradation of p27Kip1, these inhibitors aim to restore cell cycle control and induce apoptosis in malignant cells.

Other names

CKS1CKS1BCyclin-dependent kinase regulatory subunit 1Bp18NB4S

Disruption of the Skp2-Cks1 protein-protein interaction to prevent the ubiquitination and degradation of the CDK inhibitor p27Kip1 (PubMed: 22438593).