PPM1D activity promotes cellular transformation by preventing senescence and cell death

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00599728" target="_blank" >RIV/68378050:_____/24:00599728 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10486197 RIV/00216208:11310/24:10486197 RIV/00064165:_____/24:10486197
Result on the web
<a href="https://www.nature.com/articles/s41388-024-03149-3" target="_blank" >https://www.nature.com/articles/s41388-024-03149-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41388-024-03149-3" target="_blank" >10.1038/s41388-024-03149-3</a>

Result language
angličtina
Original language name
PPM1D activity promotes cellular transformation by preventing senescence and cell death
Original language description
Cell cycle checkpoints, oncogene-induced senescence and programmed cell death represent intrinsic barriers to tumorigenesis. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of the tumour suppressor p53 and has been implicated in termination of the DNA damage response. Here, we addressed the consequences of increased PPM1D activity resulting from the gain-of-function truncating mutations in exon 6 of the PPM1D. We show that while control cells permanently exit the cell cycle and reside in senescence in the presence of DNA damage caused by ionising radiation or replication stress induced by the active RAS oncogene, RPE1-hTERT and BJ-hTERT cells carrying the truncated PPM1D continue proliferation in the presence of DNA damage, form micronuclei and accumulate genomic rearrangements revealed by karyotyping. Further, we show that increased PPM1D activity promotes cell growth in the soft agar and formation of tumours in xenograft models. Finally, expression profiling of the transformed clones revealed dysregulation of several oncogenic and tumour suppressor pathways. Our data support the oncogenic potential of PPM1D in the context of exposure to ionising radiation and oncogene-induced replication stress.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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