Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00539631" target="_blank" >RIV/68378050:_____/20:00539631 - isvavai.cz</a>

Result on the web

<a href="https://www.mdpi.com/2073-4409/9/9/2068" target="_blank" >https://www.mdpi.com/2073-4409/9/9/2068</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells9092068" target="_blank" >10.3390/cells9092068</a>

Result language

angličtina

Original language name

Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Original language description

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrinsic barrier to tumorigenesis. Tumor suppressor p53 is an integral part of the checkpoints and its inactivating mutations promote cancer growth. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of p53. Although its loss impairs recovery from the G2 checkpoint and promotes induction of senescence, amplification of thePPM1Dlocus or gain-of-function truncating mutations ofPPM1Doccur in various cancers. Here we used a transgenic mouse model carrying a truncating mutation in exon 6 ofPPM1D(Ppm1d(T)). As with human cell lines, we found that the truncated PPM1D was present at high levels in the mouse thymus. Truncated PPM1D did not affect differentiation of T-cells in the thymus but it impaired their response to ionizing radiation (IR). Thymocytes inPpm1d(T/+)mice did not arrest in the checkpoint and continued to proliferate despite the presence of DNA damage. In addition, we observed a decreased level of apoptosis in the thymi ofPpm1d(T/+)mice. Moreover, the frequency of the IR-induced T-cell lymphomas increased inPpm1d(T/+)Trp53(+/-)mice resulting in decreased survival. We conclude that truncated PPM1D partially suppresses the p53 pathway in the mouse thymus and potentiates tumor formation under the condition of a partial loss of p53 function.

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

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OECD FORD branch

30204 - Oncology

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

2020

Confidentiality

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

Name of the periodical

Cells

ISSN

2073-4409

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

9

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

2068

UT code for WoS article

000580725800001

EID of the result in the Scopus database

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