WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells.
Proc Natl Acad Sci U S A
; 116(48): 23891-23893, 2019 11 26.
Article
en En
| MEDLINE
| ID: mdl-31712441
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Pirimidinonas
/
Proteínas Tirosina Quinasas
/
Fase G1
/
Proteína Quinasa CDC2
/
Fase S
/
Proteínas de Ciclo Celular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2019
Tipo del documento:
Article