WEE1分子背景
WEE1 is a serine/threonine protein kinase that acts as a critical regulator of the cell cycle, particularly at the G₂/M checkpoint. It inhibits cell cycle progression by phosphorylating and inactivating CDK1 (Cyclin-Dependent Kinase 1) at Tyr15, thereby preventing premature entry into mitosis and allowing time for DNA repair.Originally identified in fission yeast, WEE1 is highly conserved in mammals and plays a key role in maintaining genomic stability. Dysregulation of WEE1 is linked to cancer progression, as its overexpression in tumors (e.g., ovarian, breast, pancreatic cancers) supports cancer cell survival by enabling DNA damage tolerance. This dependency makes WEE1 a promising therapeutic target, especially in p53-mutant cancers where inhibiting WEE1 induces synthetic lethality by forcing cells with unrepaired DNA into catastrophic mitosis.