Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F14%3A%230000562" target="_blank" >RIV/00209805:_____/14:#0000562 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.nature.com/ncomms/2014/141008/ncomms6067/full/ncomms6067.html" target="_blank" >http://www.nature.com/ncomms/2014/141008/ncomms6067/full/ncomms6067.html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ncomms6067" target="_blank" >10.1038/ncomms6067</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A

Popis výsledku v původním jazyce

Endoplasmic reticulum (ER) stress occurs in poorly perfused tissues and activates the p53 isoform p53/47 to promote G2 arrest via 14-3-3s. This contrasts with the p21CDKN1A-dependent G1 arrest caused by p53 following DNA damage. It is not known how cellsrespond to conditions when both pathways are activated. Here we show that p53/47 prevents p53-induced p21 transcription during ER stress and that both isoforms repress p21 mRNA translation. This prevents p21 from promoting constitutive photomorphogenic1-mediated 14-3-3s degradation and leads to G2 arrest. DNA damage does not result in p53-dependent induction of p21 during ER stress and instead results in an increase in p53-induced apoptosis. This illustrates how p53 isoforms target an intrinsic balance between the G1 and G2 checkpoints for cell cycle coordination and demonstrates an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs.

Název v anglickém jazyce

Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A

Popis výsledku anglicky

Endoplasmic reticulum (ER) stress occurs in poorly perfused tissues and activates the p53 isoform p53/47 to promote G2 arrest via 14-3-3s. This contrasts with the p21CDKN1A-dependent G1 arrest caused by p53 following DNA damage. It is not known how cellsrespond to conditions when both pathways are activated. Here we show that p53/47 prevents p53-induced p21 transcription during ER stress and that both isoforms repress p21 mRNA translation. This prevents p21 from promoting constitutive photomorphogenic1-mediated 14-3-3s degradation and leads to G2 arrest. DNA damage does not result in p53-dependent induction of p21 during ER stress and instead results in an increase in p53-induced apoptosis. This illustrates how p53 isoforms target an intrinsic balance between the G1 and G2 checkpoints for cell cycle coordination and demonstrates an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs.

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/ED2.1.00%2F03.0101" target="_blank" >ED2.1.00/03.0101: Regionální centrum aplikované molekulární onkologie (RECAMO)</a><br>

Návaznosti

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

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Nature communications

ISSN

2041-1723

e-ISSN

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Svazek periodika

5

Číslo periodika v rámci svazku

8 October

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

5067

Kód UT WoS článku

000343977100002

EID výsledku v databázi Scopus

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