p53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F17%3A00077904" target="_blank" >RIV/00209805:_____/17:00077904 - isvavai.cz</a>

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596431/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596431/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/cdd.2017.96" target="_blank" >10.1038/cdd.2017.96</a>

Result language

angličtina

Original language name

p53-mediated suppression of BiP triggers BIK-induced apoptosis during prolonged endoplasmic reticulum stress

Original language description

Physiological and pathological conditions that affect the folding capacity of the endoplasmic reticulum (ER) provoke ER stress and trigger the unfolded protein response (UPR). The UPR aims to either restore the balance between newly synthesized and misfolded proteins or if the damage is severe, to trigger cell death. However, the molecular events underlying the switch between repair and cell death are not well understood. The ER-resident chaperone BiP governs the UPR by sensing misfolded proteins and thereby releasing and activating the three mediators of the UPR: PERK, IRE1 and ATF6. PERK promotes G2 cell cycle arrest and cellular repair by inducing the alternative translated p53 isoform p53ΔN40 (p53/47), which activates 14-3-3σ via suppression of p21CDKN1A. Here we show that prolonged ER stress promotes apoptosis via a p53-dependent inhibition of BiP expression. This leads to the release of the pro-apoptotic BH3-only BIK from BiP and activation of apoptosis. Suppression of bip mRNA translation is mediated via the specific binding of p53 to the first 346-nt of the bip mRNA and via a p53 trans-suppression domain located within the first seven N-terminal amino acids of p53ΔN40. This work shows how p53 targets BiP to promote apoptosis during severe ER stress and further illustrates how regulation of mRNA translation has a key role in p53-mediated regulation of gene expression during the UPR.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Cell death and differentiation

ISSN

1350-9047

e-ISSN

—

Volume of the periodical

24

Issue of the periodical within the volume

10

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

"1717–1729"

UT code for WoS article

000410166300006

EID of the result in the Scopus database

2-s2.0-85029213542