WEE1 kinase is the gatekeeper of the G2–M cell-cycle checkpoint that allows DNA repair before mitotic entry. WEE1 is highly expressed and active in several cancer types that depend on a functional G2–M checkpoint for DNA repair.
What type of kinase is WEE1?
Wee1 is a serine/threonine kinase which responds to single or double strand breaks generated by DNA damage, and causes G2-M cell cycle arrest by inactivating CDK1 (also known as CDC2) through phosphorylation of the Tyr15 residue .
How does WEE1 inhibitor work?
WEE1/PKMYT1 kinase inhibition causes G2/M cell cycle checkpoint override, premature mitotic entry, and cell death during mitosis, through a mechanism generally known as mitotic catastrophe (Fig. 4a).21 Sept 2020
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].26 Mar 2013
Which proteins does Wee1 control?
Wee1 is a protein kinase that regulates the G2 checkpoint and prevents entry into mitosis in response to DNA damage (Fig. 1; ref. 1). The cell cycle is a highly controlled process.15 Aug 2017
What is a wee 1 inhibitor?
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.18 Jun 2020
What does Wee1 protein do?
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.
What does the wee 1 kinase do?
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.26 Aug 2013
What do Wee1 and CAK do?
The decreased Wee1 activity alone is not sufficient for mitotic entry: Synthesis of cyclins and an activating phosphorylation by a Cdk activating kinase (CAK) are also required. Wee1 plays a role in this checkpoint by coordinating cell size and cell cycle progression.
What kind of kinase is Wee1?
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.
Is Cdc25 a kinase?
Calcium/calmodulin-dependent protein kinase (CaM kinase II) KN-93-induced inhibition of phosphorylation of CDC25C inhibited progression of the cells through the G2/M phase checkpoint. CDC25C protein is a substrate for CaM kinase II, and its phosphorylation increases its phosphatase activity.2 Apr 2016