@article{Roverato2021-03-16Parki-53205,
  year={2021},
  doi={10.1016/j.celrep.2021.108857},
  title={Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy},
  number={11},
  volume={34},
  journal={Cell Reports},
  author={Roverato, Nicola D. and Sailer, Carolin and Catone, Nicola and Aichem, Annette and Stengel, Florian and Gröttrup, Marcus},
  note={Article Number: 108857}
}

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    <dcterms:abstract xml:lang="eng">Parkin is an E3 ubiquitin ligase belonging to the RING-between-RING family. Mutations in the Parkin-encoding gene PARK2 are associated with familial Parkinson's disease. Here, we investigate the interplay between Parkin and the inflammatory cytokine-induced ubiquitin-like modifier FAT10. FAT10 targets hundreds of proteins for degradation by the 26S proteasome. We show that FAT10 gets conjugated to Parkin and mediates its degradation in a proteasome-dependent manner. Parkin binds to the E2 enzyme of FAT10 (USE1), auto-FAT10ylates itself, and facilitates FAT10ylation of the Parkin substrate Mitofusin2 in vitro and in cells, thus identifying Parkin as a FAT10 E3 ligase. On mitochondrial depolarization, FAT10ylation of Parkin inhibits its activation and ubiquitin-ligase activity causing impairment of mitophagy progression and aggravation of rotenone-mediated death of dopaminergic neuronal cells. In conclusion, FAT10ylation inhibits Parkin and mitophagy rendering FAT10 a likely inflammation-induced exacerbating factor and potential drug target for Parkinson's disease.</dcterms:abstract>
    <dc:contributor>Catone, Nicola</dc:contributor>
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    <dc:contributor>Stengel, Florian</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:creator>Roverato, Nicola D.</dc:creator>
    <dc:creator>Sailer, Carolin</dc:creator>
    <dc:creator>Stengel, Florian</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/53205"/>
    <dc:contributor>Roverato, Nicola D.</dc:contributor>
    <dc:language>eng</dc:language>
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    <dc:contributor>Gröttrup, Marcus</dc:contributor>
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    <dc:creator>Aichem, Annette</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-03-19T12:58:17Z</dc:date>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dcterms:issued>2021-03-16</dcterms:issued>
    <dcterms:title>Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy</dcterms:title>
    <dc:contributor>Sailer, Carolin</dc:contributor>
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    <dc:creator>Gröttrup, Marcus</dc:creator>
    <dc:creator>Catone, Nicola</dc:creator>
    <dc:contributor>Aichem, Annette</dc:contributor>
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