What does Wee1 kinase do?
Wee1 Kinase. 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.
Why is a wee kinase inhibitor used in cancer therapy trials?
The initial clinical development of the Wee1 inhibitor, MK-1775, has been to chemopotentiate the DNA damaging effects of chemotherapy, utilizing the concept of mitotic lethality as a mechanism for antitumor activity based on early in vitro studies demonstrating its role in regulation of Cdk1 and the G2 checkpoint.
Which protein kinase directly inhibits Wee1 activity?
pombe, Pom1, a protein kinase, localizes to the cell poles. This activates a pathway in which Cdr2 inhibits Wee1 through Cdr1.
What is the substrate for the Wee1 kinase?
In rheumatoid synovial cells, wee1 kinase was increased in conjunction with the increase of c-Fos/AP-1 and the substrate of wee1, cdc2, was phosphorylated. The amount of wee1 and c-Fos and the phosphorylation of cdc2 were decreased after treatment of the cells with an inhibitor of AP-1, curcumin.
What is Wee1 inhibitor?
It has been proposed that WEE1 inhibitor promotes cancer cells to prematurely enter mitosis as a result of bypassing the G2 cell-cycle checkpoint [6] as well as delays mitotic exit, resulting in mitotic arrest [7].
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 WEE1 inhibitor?
What are Chk1 and Chk2?
Function. Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. Chk1 is a central component of genome surveillance pathways and is a key regulator of the cell cycle and cell survival.
What is mitotic cell death?
Mitotic catastrophe (MC) has long been considered as a mode of cell death that results from premature or inappropriate entry of cells into mitosis and can be caused by chemical or physical stresses.
How do Chk1 inhibitors work?
By inhibiting Chk1, cancer cells lose the ability to repair damaged DNA which allows chemotherapeutic agents to work more effectively. Combining DNA damaging therapies such as chemotherapy or radiation treatment with Chk1 inhibition enhances targeted cell death and provides synthetic lethality.
How does Chk1 affect the cell cycle?
In unperturbed cell cycle, Chk1 regulates DNA replication in S phase, G2/M transition or mitotic entry, and spindle checkpoint in M phase (Fig. 3). In S phase, Chk1 arrests cell cycle for DNA replication mainly by inducing Cdc25A degradation, resulting in the inhibition of CDK2.