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Statements

Subject Item
n2:RIV%2F00209805%3A_____%2F14%3A%230000562%21RIV15-MSM-00209805
rdf:type
skos:Concept n15:Vysledek
rdfs:seeAlso
http://www.nature.com/ncomms/2014/141008/ncomms6067/full/ncomms6067.html
dcterms:description
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 cells respond 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 photomorphogenic 1-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. 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 cells respond 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 photomorphogenic 1-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.
dcterms:title
Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A
skos:prefLabel
Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A
skos:notation
RIV/00209805:_____/14:#0000562!RIV15-MSM-00209805
n6:aktivita
n8:P
n6:aktivity
P(ED2.1.00/03.0101)
n6:cisloPeriodika
8 October
n6:dodaniDat
n12:2015
n6:domaciTvurceVysledku
Fåhraeus, Robin
n6:druhVysledku
n10:J
n6:duvernostUdaju
n13:S
n6:entitaPredkladatele
n17:predkladatel
n6:idSjednocenehoVysledku
14530
n6:idVysledku
RIV/00209805:_____/14:#0000562
n6:jazykVysledku
n16:eng
n6:klicovaSlova
messenger-RNA translation; ubiquitin ligase COP1; tumor suppressor; p53 isoforms; hepatocellular carcinoma; negative ragulator; growth arrest; up-regulation
n6:klicoveSlovo
n7:hepatocellular%20carcinoma n7:messenger-RNA%20translation n7:p53%20isoforms n7:growth%20arrest n7:tumor%20suppressor n7:ubiquitin%20ligase%20COP1 n7:up-regulation n7:negative%20ragulator
n6:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n6:kontrolniKodProRIV
[DCC9DFBA2309]
n6:nazevZdroje
Nature communications
n6:obor
n18:EB
n6:pocetDomacichTvurcuVysledku
1
n6:pocetTvurcuVysledku
2
n6:projekt
n9:ED2.1.00%2F03.0101
n6:rokUplatneniVysledku
n12:2014
n6:svazekPeriodika
5
n6:tvurceVysledku
Fåhraeus, Robin Mlynarczyk, C.
n6:wos
000343977100002
s:issn
2041-1723
s:numberOfPages
16
n11:doi
10.1038/ncomms6067