DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F15%3A00442490" target="_blank" >RIV/68378050:_____/15:00442490 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.4161/15384101.2014.988019" target="_blank" >http://dx.doi.org/10.4161/15384101.2014.988019</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4161/15384101.2014.988019" target="_blank" >10.4161/15384101.2014.988019</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

Popis výsledku v původním jazyce

Death domain-associated protein 6 (DAXX) is a histone chaperone, putative regulator of apoptosis and transcription, and candidate modulator of p53-mediated gene expression following DNA damage. DAXX becomes phosphorylated upon DNA damage, however regulation of this modification, and its relationship to p53 remain unclear. Here we show that in human cells exposed to ionizing radiation or genotoxic drugs etoposide and neocarzinostatin, DAXX became rapidly phosphorylated in an ATM kinase-dependent manner.Our deletion and site-directed mutagenesis experiments identified Serine 564 (S564) as the dominant ATM-targeted site of DAXX, and immunofluorescence experiments revealed localization of S564-phosphorylated DAXX to PML nuclear bodies. Furthermore, usinga panel of human cell types, we identified the p53-regulated Wip1 protein phosphatase as a key negative regulator of DAXX phosphorylation at S564, both in vitro and in cells. Consistent with the emerging oncogenic role of Wip1, its DAXX-d

Název v anglickém jazyce

DNA damage-induced regulatory interplay between DAXX, p53, ATM kinase and Wip1 phosphatase

Popis výsledku anglicky

Death domain-associated protein 6 (DAXX) is a histone chaperone, putative regulator of apoptosis and transcription, and candidate modulator of p53-mediated gene expression following DNA damage. DAXX becomes phosphorylated upon DNA damage, however regulation of this modification, and its relationship to p53 remain unclear. Here we show that in human cells exposed to ionizing radiation or genotoxic drugs etoposide and neocarzinostatin, DAXX became rapidly phosphorylated in an ATM kinase-dependent manner.Our deletion and site-directed mutagenesis experiments identified Serine 564 (S564) as the dominant ATM-targeted site of DAXX, and immunofluorescence experiments revealed localization of S564-phosphorylated DAXX to PML nuclear bodies. Furthermore, usinga panel of human cell types, we identified the p53-regulated Wip1 protein phosphatase as a key negative regulator of DAXX phosphorylation at S564, both in vitro and in cells. Consistent with the emerging oncogenic role of Wip1, its DAXX-d

Druh

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

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/GPP305%2F11%2FP683" target="_blank" >GPP305/11/P683: Posttranslační modifikace Daxxu a jejich funkční význam při poškození DNA a buněčné senescenci</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Cell Cycle

ISSN

1538-4101

e-ISSN

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Svazek periodika

14

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

375-387

Kód UT WoS článku

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EID výsledku v databázi Scopus

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