Cyclin-dependent kinase-like 3 (CDKL3)

Cyclin-dependent kinase-like 3 (CDKL3) is a serine/threonine protein kinase belonging to the cyclin-dependent kinase-like subfamily, which is part of the CMGC kinase superfamily[1][2]. CDKL3 primarily localizes to the nucleus and is involved in regulating cell cycle progression, notably by interacting with cyclins—especially cyclin A2—to promote phosphorylation of the retinoblastoma protein (Rb), leading to cell cycle entry and proliferation[1]. CDKL3 can also stabilize CDK4 by phosphorylating it, protecting it from ubiquitin-mediated degradation[1]. Overexpression of CDKL3 has been linked to several cancers, functioning as an oncogene by promoting proliferation, migration, and resistance to certain cell cycle inhibitors[2][3]. CDKL3 expression is a promising biomarker for cancer diagnosis and prognosis, especially in hepatocellular carcinoma and glioma[2][3]. Small molecule inhibitors targeting CDKL3 (such as HZ1) are being explored as anticancer agents, but further studies are needed to determine safety and therapeutic window[1].

Other names

CDKL3NKIAMRESerine/threonine-protein kinase NKIAMRE

Inhibition of CDKL3 kinase activity (e.g., HZ1 blocks CDKL3, leading to cell cycle arrest in cancer cells); Downregulation/inhibition reduces tumor cell proliferation and induces apoptosis