What does Wee1 mean?
Mitosis inhibitor protein
Symbol. Mitosis inhibitor protein kinase Wee1.
What is the function of WEE 1?
Wee1 is a nuclear protein involved in the regulation of the G2/M checkpoint by negatively regulating entry into mitosis by catalyzing an inhibitory tyrosine phosphorylation of the Cdc2/cyclin B kinase complex.
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]. It was first discovered 25 years ago as a cell division cycle (cdc) mutant-wee1- in the fission yeast, Schizosaccharomyces pombe [26].
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.
Is Wee1 a phosphatase?
Wee1 is a kinase that delays mitosis via inhibitory phosphorylation of Cdk1, while Cdc25 is a phosphatase that promotes mitosis by removing the inhibitory phosphorylation. Although Wee1 and Cdc25 are conserved proteins, it has remained unclear whether their functions and regulation are conserved across diverse species.
Is Wee1 a tumor suppressor?
What is Zn c3?
Introduction: ZN-c3 is a selective and orally bioavailable small molecule WEE1 inhibitor. WEE1 is a crucial component of the G2/M cell cycle checkpoint preventing cells from entering mitosis to allow repair of DNA damage before cell cycle progression.
Where is the WEE1 gene located in the body?
The human WEE1 gene is located on 11p15.3-p15.1 ( 18 ), and the 646–amino acid protein contains 3 domains: an N -terminal regulatory domain, a central kinase domain, and a short C-terminal regulatory domain ( 19 ). The kinase domain seems to be strictly specific for phosphorylation of Y15 of CDK1 in vivo ( 3, 5, 8 ).
What are the side effects of Wee1 inhibition?
Dose-limiting toxicity consisted of hematologic events, nausea and/or vomiting, and fatigue. The combination of DNA-damaging cancer therapy with WEE1 inhibition seems to be a rational approach to push cancer cells in mitotic catastrophe. Its safety and efficacy are being evaluated in clinical studies.
Why is Wee1 kinase important in the cell cycle?
WEE1 kinase is a key molecule in maintaining G 2 –cell-cycle checkpoint arrest for premitotic DNA repair. Whereas normal cells repair damaged DNA during G 1 -arrest, cancer cells often have a deficient G 1 -arrest and largely depend on G 2 -arrest.
Can a Wee1 inhibitor be used for cancer treatment?
One WEE1 inhibitor has now reached clinical phase I studies. Dose-limiting toxicity consisted of hematologic events, nausea and/or vomiting, and fatigue. The combination of DNA-damaging cancer therapy with WEE1 inhibition seems to be a rational approach to push cancer cells in mitotic catastrophe.