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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

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

Popis výsledku anglicky

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

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

<a href="/cs/project/ED0030%2F01%2F01" target="_blank" >ED0030/01/01: Biomedicína pro regionální rozvoj a lidské zdroje</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Nature Cell Biology

ISSN

1465-7392

e-ISSN

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Svazek periodika

15

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

967-977

Kód UT WoS článku

000322570900013

EID výsledku v databázi Scopus

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