WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31712441.
- Also identified by DOI 10.1073/pnas.1915108116 and PMC identifier 6883772.
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Abstract
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.
Medical subject headings
- CDC2 Protein Kinase
- Cell Cycle Proteins
- G1 Phase
- Protein-Tyrosine Kinases
- Pyrazoles
- Pyrimidinones
- S Phase