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  • 标题:WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
  • 本地全文:下载
  • 作者:Tatiana N. Moiseeva ; Chenao Qian ; Norie Sugitani
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:48
  • 页码:23891-23893
  • DOI:10.1073/pnas.1915108116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:WEE1 ; cell cycle ; DNA replication ; CDK1 ; RIF1
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