CDK1 is a serine/threonine kinase that serves as the master regulator of mitotic entry and cell cycle progression. Primary function: CDK1 activation triggered by Cyclin B binding drives the G2/M transition and entry into mitosis 1, with hundreds of mitotic proteins phosphorylated by the CDK1:Cyclin-B complex 2. Mechanism: CDK1 phosphorylates multiple substrates at specific residues—for example, phosphorylating pVHL at Ser80 to prime PIN1 recognition 3, and phosphorylating lamins to facilitate their depolymerization during mitosis via SETD2-mediated scaffold assembly 4. Disease relevance: CDK1 overexpression drives tumorigenesis across multiple cancer types. In triple-negative breast cancer, deubiquitylase YOD1 stabilizes CDK1 protein expression, promoting proliferation and chemotherapy resistance 5. Similarly, OTUD4-mediated CDK1 stabilization activates MAPK signaling in glioblastoma 6. In colorectal cancer, CDK1 suppresses ferroptosis by phosphorylating and degrading ACSL4, conferring oxaliplatin resistance 7. Clinical significance: CDK1 inhibition represents a therapeutic strategy; PKMYT1 inhibition (which unleashes CDK1) shows synthetic lethality in CCNE1-amplified cancers 8, while direct CDK1 inhibition combined with chemotherapy improves outcomes in resistant tumors 75.