Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway. / Petrosius, Valdemaras; Benada, Jan; Nielsen, Olaf; Schoof, Erwin M.; Sørensen, Claus Storgaard.

In: iScience, Vol. 26, No. 1, 105806, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Petrosius, V, Benada, J, Nielsen, O, Schoof, EM & Sørensen, CS 2023, 'Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway', iScience, vol. 26, no. 1, 105806. https://doi.org/10.1016/j.isci.2022.105806

APA

Petrosius, V., Benada, J., Nielsen, O., Schoof, E. M., & Sørensen, C. S. (2023). Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway. iScience, 26(1), [105806]. https://doi.org/10.1016/j.isci.2022.105806

Vancouver

Petrosius V, Benada J, Nielsen O, Schoof EM, Sørensen CS. Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway. iScience. 2023;26(1). 105806. https://doi.org/10.1016/j.isci.2022.105806

Author

Petrosius, Valdemaras ; Benada, Jan ; Nielsen, Olaf ; Schoof, Erwin M. ; Sørensen, Claus Storgaard. / Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway. In: iScience. 2023 ; Vol. 26, No. 1.

Bibtex

@article{42609ed00378455a9137832339678f3b,

title = "Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway",

abstract = "Wee1-like protein kinase (WEE1) restrains activities of cyclin-dependent kinases (CDKs) in S and G2 phase. Inhibition of WEE1 evokes drastic increase in CDK activity, which perturbs replication dynamics and compromises cell cycle checkpoints. Notably, WEE1 inhibitors such as adavosertib are tested in cancer treatment trials; however, WEE1-regulated phosphoproteomes and their dynamics have not been systematically investigated. In this study, we identified acute time-resolved alterations in the cellular phosphoproteome following WEE1 inhibition with adavosertib. These treatments acutely elevated CDK activities with distinct phosphorylation dynamics revealing more than 600 potential uncharacterized CDK sites. Moreover, we identified a major role for WEE1 in controlling CDK-dependent phosphorylation of multiple clustered sites in the key DNA repair factors MDC1, 53BP1, and RIF1. Functional analysis revealed that WEE1 fine-tunes CDK activities to permit recruitment of 53BP1 to chromatin. Thus, our findings uncover WEE1-controlled targets and pathways with translational potential for the clinical application of WEE1 inhibitors.",

keywords = "Cancer, Molecular biology, Omics",

author = "Valdemaras Petrosius and Jan Benada and Olaf Nielsen and Schoof, {Erwin M.} and S{\o}rensen, {Claus Storgaard}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2023",

doi = "10.1016/j.isci.2022.105806",

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier",

number = "1",

}

RIS

TY - JOUR

T1 - Temporal phosphoproteomics reveals WEE1-dependent control of 53BP1 pathway

AU - Petrosius, Valdemaras

AU - Benada, Jan

AU - Nielsen, Olaf

AU - Schoof, Erwin M.

AU - Sørensen, Claus Storgaard

PY - 2023

Y1 - 2023

N2 - Wee1-like protein kinase (WEE1) restrains activities of cyclin-dependent kinases (CDKs) in S and G2 phase. Inhibition of WEE1 evokes drastic increase in CDK activity, which perturbs replication dynamics and compromises cell cycle checkpoints. Notably, WEE1 inhibitors such as adavosertib are tested in cancer treatment trials; however, WEE1-regulated phosphoproteomes and their dynamics have not been systematically investigated. In this study, we identified acute time-resolved alterations in the cellular phosphoproteome following WEE1 inhibition with adavosertib. These treatments acutely elevated CDK activities with distinct phosphorylation dynamics revealing more than 600 potential uncharacterized CDK sites. Moreover, we identified a major role for WEE1 in controlling CDK-dependent phosphorylation of multiple clustered sites in the key DNA repair factors MDC1, 53BP1, and RIF1. Functional analysis revealed that WEE1 fine-tunes CDK activities to permit recruitment of 53BP1 to chromatin. Thus, our findings uncover WEE1-controlled targets and pathways with translational potential for the clinical application of WEE1 inhibitors.

AB - Wee1-like protein kinase (WEE1) restrains activities of cyclin-dependent kinases (CDKs) in S and G2 phase. Inhibition of WEE1 evokes drastic increase in CDK activity, which perturbs replication dynamics and compromises cell cycle checkpoints. Notably, WEE1 inhibitors such as adavosertib are tested in cancer treatment trials; however, WEE1-regulated phosphoproteomes and their dynamics have not been systematically investigated. In this study, we identified acute time-resolved alterations in the cellular phosphoproteome following WEE1 inhibition with adavosertib. These treatments acutely elevated CDK activities with distinct phosphorylation dynamics revealing more than 600 potential uncharacterized CDK sites. Moreover, we identified a major role for WEE1 in controlling CDK-dependent phosphorylation of multiple clustered sites in the key DNA repair factors MDC1, 53BP1, and RIF1. Functional analysis revealed that WEE1 fine-tunes CDK activities to permit recruitment of 53BP1 to chromatin. Thus, our findings uncover WEE1-controlled targets and pathways with translational potential for the clinical application of WEE1 inhibitors.

KW - Cancer

KW - Molecular biology

KW - Omics

U2 - 10.1016/j.isci.2022.105806

DO - 10.1016/j.isci.2022.105806

M3 - Journal article

C2 - 36632060

AN - SCOPUS:85145279484

VL - 26

JO - iScience

JF - iScience

SN - 2589-0042

IS - 1

M1 - 105806

ER -

ID: 331716265

Department of Biology