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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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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

2014

Confidentiality

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

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

Aug 21

Country of publishing house

GB - UNITED KINGDOM

Number of pages

11

Pages from-to

4706

UT code for WoS article

000341078900004

EID of the result in the Scopus database

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