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Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy

Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy

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ROVERATO, Nicola D., Carolin SAILER, Nicola CATONE, Annette AICHEM, Florian STENGEL, Marcus GROETTRUP, 2021. Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy. In: Cell Reports. Cell Press. 34(11), 108857. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2021.108857

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

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/53205"> <dc:creator>Stengel, Florian</dc:creator> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-03-19T12:58:17Z</dcterms:available> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-03-19T12:58:17Z</dc:date> <dc:contributor>Roverato, Nicola D.</dc:contributor> <dc:contributor>Groettrup, Marcus</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Sailer, Carolin</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/53205/1/Parkin_2-jpy86fkp1vqj3.pdf"/> <dc:creator>Aichem, Annette</dc:creator> <dc:contributor>Sailer, Carolin</dc:contributor> <dc:rights>Attribution 4.0 International</dc:rights> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Catone, Nicola</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/53205"/> <dcterms:issued>2021-03-16</dcterms:issued> <dc:contributor>Stengel, Florian</dc:contributor> <dc:creator>Roverato, Nicola D.</dc:creator> <dc:creator>Catone, Nicola</dc:creator> <dc:contributor>Aichem, Annette</dc:contributor> <dcterms:title>Parkin is an E3 ligase for the ubiquitin-like modifier FAT10, which inhibits Parkin activation and mitophagy</dcterms:title> <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:creator>Groettrup, Marcus</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/53205/1/Parkin_2-jpy86fkp1vqj3.pdf"/> <dc:language>eng</dc:language> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> </rdf:Description> </rdf:RDF>

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