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

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About: Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://www.nature.com/ncomms/2014/141008/ncomms6067/full/ncomms6067.html
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. (en)
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 (en)
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 (en)
skos:notation	RIV/00209805:_____/14:#0000562!RIV15-MSM-00209805
http://linked.open...avai/riv/aktivita	P
http://linked.open...avai/riv/aktivity	P(ED2.1.00/03.0101)
http://linked.open...iv/cisloPeriodika	8 October
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Fåhraeus, Robin
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Masarykův onkologický ústav
http://linked.open...dnocenehoVysledku	14530
http://linked.open...ai/riv/idVysledku	RIV/00209805:_____/14:#0000562
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	messenger-RNA translation; ubiquitin ligase COP1; tumor suppressor; p53 isoforms; hepatocellular carcinoma; negative ragulator; growth arrest; up-regulation (en)
http://linked.open.../riv/klicoveSlovo	growth arrest messenger-RNA translation negative ragulator p53 isoforms ubiquitin ligase COP1 tumor suppressor hepatocellular carcinoma up-regulation
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[DCC9DFBA2309]
http://linked.open...i/riv/nazevZdroje	Nature communications
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	2 (xsd:int)
http://linked.open...vavai/riv/projekt	Regional Centre for Applied Molecular Oncology (RECAMO)
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	5
http://linked.open...iv/tvurceVysledku	Fåhraeus, Robin Mlynarczyk, C.
http://linked.open...ain/vavai/riv/wos	000343977100002
issn	2041-1723
number of pages	16 (xsd:int)
http://bibframe.org/vocab/doi	10.1038/ncomms6067

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