Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of CDKN1A
Original language 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 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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/ED2.1.00%2F03.0101" target="_blank" >ED2.1.00/03.0101: Regional Centre for Applied Molecular Oncology (RECAMO)</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2014
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature communications
ISSN
2041-1723
e-ISSN
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Volume of the periodical
5
Issue of the periodical within the volume
8 October
Country of publishing house
GB - UNITED KINGDOM
Number of pages
16
Pages from-to
5067
UT code for WoS article
000343977100002
EID of the result in the Scopus database
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