WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells

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 CD...

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Autores principales: Moiseeva, Tatiana N., Qian, Chenao, Sugitani, Norie, Osmanbeyoglu, Hatice U., Bakkenist, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Biological Sciences
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883772/
https://www.ncbi.nlm.nih.gov/pubmed/31712441
http://dx.doi.org/10.1073/pnas.1915108116
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author Moiseeva, Tatiana N.
Qian, Chenao
Sugitani, Norie
Osmanbeyoglu, Hatice U.
Bakkenist, Christopher J.
author_facet Moiseeva, Tatiana N.
Qian, Chenao
Sugitani, Norie
Osmanbeyoglu, Hatice U.
Bakkenist, Christopher J.
author_sort Moiseeva, Tatiana N.
collection PubMed
description 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.
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spelling pubmed-68837722019-12-04 WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells Moiseeva, Tatiana N. Qian, Chenao Sugitani, Norie Osmanbeyoglu, Hatice U. Bakkenist, Christopher J. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2019-11-26 2019-11-11 /pmc/articles/PMC6883772/ /pubmed/31712441 http://dx.doi.org/10.1073/pnas.1915108116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Moiseeva, Tatiana N.
Qian, Chenao
Sugitani, Norie
Osmanbeyoglu, Hatice U.
Bakkenist, Christopher J.
WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title_full WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title_fullStr WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title_full_unstemmed WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title_short WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells
title_sort wee1 kinase inhibitor azd1775 induces cdk1 kinase-dependent origin firing in unperturbed g1- and s-phase cells
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883772/
https://www.ncbi.nlm.nih.gov/pubmed/31712441
http://dx.doi.org/10.1073/pnas.1915108116
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