Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F13%3A33144906" target="_blank" >RIV/61989592:15110/13:33144906 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/ncb2795" target="_blank" >http://dx.doi.org/10.1038/ncb2795</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/ncb2795" target="_blank" >10.1038/ncb2795</a>

Result language
angličtina
Original language name
Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer
Original language description
The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR. Contrary to either scenario,we found that in human oncogene-transformed and cancer cells, ATM suppressed ARF protein levels and activity in a transcription-independent manner. Mechanistically, ATM activated protein phosphatase 1, which antagonized Nek2-dependent phosphorylation ofnucleophosmin (NPM), thereby liberating ARF from NPM and rendering it susceptible to degradation by the ULF E3-ubiquitin ligase. In human clinical samples, loss of ATM expression correlated with increased ARF levels and in xenograft and tissue culture models, inhibition of ATM stimulated the tumour-suppressive effects of ARF. These results provide insights into the functional interplay between the DDR and ARF anti-cancer barriers, with implications for tumorigenesis and treatment of adv
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Project
<a href="/en/project/ED0030%2F01%2F01" target="_blank" >ED0030/01/01: Biomedicine for regional development and human resources</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2013
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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