Figures & data
Figure 1 WEE1 kinase in cell cycle regulation and DNA damage repair. ATR or ATM are employed during the G2/M checkpoint to detect DNA damage, depending on the type of genotoxic stress. The phosphorylation of ATR leads to activation of CHK1, which subsequently activates WEE1 and inactivates CDC25. Active WEE1 phosphorylates the CDK1-CyclinB complex at tyrosine 15, keeping the complex inactive and preventing cells from entering mitosis. The activation of ATM phosphorylates and activates CHK2, and subsequently promotes the cytoplasmic sequestration and inactivation of CDC25, which reduces the CDK1 activity and prevents cells entry into mitosis. After DNA damage repair, WEE1 activity is attenuated, the inhibitory phosphorylation of CDK1 is prevented, and the inhibitory effect of CHK1 and CHK2 on CDC25 is abolished. CDC25 dephosphorylates CDK1-CylinB, activates the complex, and drives cells into mitosis.
Table 1 WEE1 Inhibitor in Gynecologic Oncology Clinical Trials