PPM1D activity promotes the replication stress caused by cyclin E1 overexpression

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00578357" target="_blank" >RIV/68378050:_____/24:00578357 - isvavai.cz</a>

Result on the web

<a href="https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13433" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13433</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/1878-0261.13433" target="_blank" >10.1002/1878-0261.13433</a>

Result language

angličtina

Original language name

PPM1D activity promotes the replication stress caused by cyclin E1 overexpression

Original language description

Oncogene-induced replication stress has been recognized as a major cause of genome instability in cancer cells. Increased expression of cyclin E1 caused by amplification of the CCNE1 gene is a common cause of replication stress in various cancers. Protein phosphatase magnesium-dependent 1 delta (PPM1D) is a negative regulator of p53 and has been implicated in termination of the cell cycle checkpoint. Amplification of the PPM1D gene or frameshift mutations in its final exon promote tumorigenesis. Here, we show that PPM1D activity further increases the replication stress caused by overexpression of cyclin E1. In particular, we demonstrate that cells expressing a truncated mutant of PPM1D progress faster from G1 to S phase and fail to complete licensing of the replication origins. In addition, we show that transcription-replication collisions and replication fork slowing caused by CCNE1 overexpression are exaggerated in cells expressing the truncated PPM1D. Finally, replication speed and accumulation of focal DNA copy number alterations caused by induction of CCNE1 expression was rescued by pharmacological inhibition of PPM1D. We propose that increased activity of PPM1D suppresses the checkpoint function of p53 and thus promotes genome instability in cells expressing the CCNE1 oncogene.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Oncology

ISSN

1574-7891

e-ISSN

1878-0261

Volume of the periodical

18

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

6-20

UT code for WoS article

001084923200001

EID of the result in the Scopus database

2-s2.0-85174264261