Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F14%3A%230000553" target="_blank" >RIV/00209805:_____/14:#0000553 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.nature.com/ncomms/2014/140821/ncomms5706/full/ncomms5706.html" target="_blank" >http://www.nature.com/ncomms/2014/140821/ncomms5706/full/ncomms5706.html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ncomms5706" target="_blank" >10.1038/ncomms5706</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence

Popis výsledku v původním jazyce

Del133p53alpha, a p53 isoform that can inhibit full-length p53, is downregulated at replicative senescence in a manner independent of mRNA regulation and proteasome-mediated degradation. Here we demonstrate that, unlike full-length p53, del133p53alpha isdegraded by autophagy during replicative senescence. Pharmacological inhibition of autophagy restores del133p53alpha expression levels in replicatively senescent fibroblasts, without affecting full-length p53. The siRNA-mediated knockdown of pro-autophagic proteins (ATG5, ATG7 and Beclin-1) also restores del133p53alpha expression. The chaperone-associated E3 ubiquitin ligase STUB1, which is known to regulate autophagy, interacts with del133p53alpha and is downregulated at replicative senescence. The siRNA knockdown of STUB1 in proliferating, early-passage fibroblasts induces the autophagic degradation of del133p53alpha and thereby induces senescence. Upon replicative senescence or STUB1 knockdown, del133p53alpha is recruited to autopha

Název v anglickém jazyce

Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence

Popis výsledku anglicky

Del133p53alpha, a p53 isoform that can inhibit full-length p53, is downregulated at replicative senescence in a manner independent of mRNA regulation and proteasome-mediated degradation. Here we demonstrate that, unlike full-length p53, del133p53alpha isdegraded by autophagy during replicative senescence. Pharmacological inhibition of autophagy restores del133p53alpha expression levels in replicatively senescent fibroblasts, without affecting full-length p53. The siRNA-mediated knockdown of pro-autophagic proteins (ATG5, ATG7 and Beclin-1) also restores del133p53alpha expression. The chaperone-associated E3 ubiquitin ligase STUB1, which is known to regulate autophagy, interacts with del133p53alpha and is downregulated at replicative senescence. The siRNA knockdown of STUB1 in proliferating, early-passage fibroblasts induces the autophagic degradation of del133p53alpha and thereby induces senescence. Upon replicative senescence or STUB1 knockdown, del133p53alpha is recruited to autopha

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

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

Aug 21

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

4706

Kód UT WoS článku

000341078900004

EID výsledku v databázi Scopus

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