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WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
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WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
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WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
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Journal Article
WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
2019
Overview
WEE1 kinase is a key regulator of the G2/M transition. The WEE1 kinase inhibitor AZD1775 (WEE1i) induces origin firing in replicating cells. We show that WEE1i induces CDK1-dependent RIF1 phosphorylation and CDK2- and CDC7-dependent activation of the replicative helicase. WEE1 suppresses CDK1 and CDK2 kinase activities to regulate the G1/S transition after the origin licensing is complete. We identify a role for WEE1 in cell cycle regulation and important effects of AZD1775, which is in clinical trials.
Publisher
National Academy of Sciences
Subject
/ CDC2 Protein Kinase - metabolism
/ Cell Cycle Checkpoints - drug effects
/ Cell Cycle Proteins - antagonists & inhibitors
/ Cell Cycle Proteins - physiology
/ Humans
/ Kinases
/ Protein-Tyrosine Kinases - antagonists & inhibitors
/ Protein-Tyrosine Kinases - physiology
