Why Wee1 kinase is a potential target for cancer therapy?
Wee1, a protein kinase, regulates the G2 checkpoint in response to DNA damage. Preclinical studies have elucidated the role of wee1 in DNA damage repair and the stabilization of replication forks, supporting the validity of wee1 inhibition as a viable therapeutic target in cancer.
Is Wee1 a tyrosine kinase?
WEE1 is an evolutionarily conserved nuclear tyrosine kinase (Table 2) that is markedly active during the S/G2 phase of the cell cycle [24, 25].
Which proteins does Wee1 control?
The Wee1 kinase regulates entry into mitosis, by negatively controlling CDK1 and 2. In a similar fashion to ATR and Chk1, it is active during normal unperturbed cell division, playing a role in the maintenance of genome integrity.
How does WEE1 inhibitor work?
WEE1 inhibition can increase genomic instability by inducing replication stress and G2/M checkpoint inactivation, which result in increased cellular sensitivity to DNA damaging agents.
What is WEE1 inhibitor?
WEE1 kinase is a serine-threonine kinase that regulates G2/M checkpoint transition [1–3]. WEE1 triggers G2/M arrest through inhibitory phosphorylation on Tyr15 of CDK1 (Cdc2) and preventing entry into mitosis to allow DNA repair during DNA damage [1–3].
Is WEE1 a tumor suppressor?
Conclusions. These results suggest that, while Wee1 acts as a tumor suppressor in the context of normal cell growth and its functional loss can be compensated by p53-dependent DNA damage repairing mechanisms, specific inhibition of Wee1 has deleterious effects on the proliferation and survival of p53 inactive tumors.
What is the phenotype of yeast cells that are WEE1 mutants?
Deficiency in wee1 causes premature mitotic entry, resulting in small size in yeast (hence the “wee” phenotype). The catalytic domain of human WEE1 (WEE1Hu) was isolated as a cDNA fragment that could complement the wee1 mutation in fission yeast (Igarashi et al. 1991).
How do WEE1 inhibitors work?
