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| rdfs:seeAlso
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| 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 is degraded 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 autophagosomes, consistent with its autophagic degradation. This study reveals that STUB1 is an endogenous regulator of del133p53alpha degradation and senescence, and identifies a p53 isoform-specific protein turnover mechanism that orchestrates p53-mediated senescence.
- 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 is degraded 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 autophagosomes, consistent with its autophagic degradation. This study reveals that STUB1 is an endogenous regulator of del133p53alpha degradation and senescence, and identifies a p53 isoform-specific protein turnover mechanism that orchestrates p53-mediated senescence. (en)
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| Title
| - Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence
- Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence (en)
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| skos:prefLabel
| - Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence
- Autophagic degradation of the inhibitory p53 isoform del133p53alpha as a regulatory mechanism for p53-mediated senescence (en)
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| skos:notation
| - RIV/00209805:_____/14:#0000553!RIV15-GA0-00209805
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - P(ED2.1.00/03.0101), P(GBP206/12/G151)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00209805:_____/14:#0000553
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| http://linked.open...riv/jazykVysledku
| |
| http://linked.open.../riv/klicovaSlova
| - chaperone-mediated autophagy; ubiquitin ligase Chip; celullar senescence; selective autophagy; down-regulation; human cells; DNA damage; mutant p53; cancer; tumorigenesis (en)
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| http://linked.open.../riv/klicoveSlovo
| |
| http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
| |
| http://linked.open...ichTvurcuVysledku
| |
| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Vojtěšek, Bořivoj
- Horikawa, Izumi
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
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| http://bibframe.org/vocab/doi
| |
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