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The ubiquitin-like modifier FAT10 stimulates the activity of the deubiquitylating enzyme OTUB1

The ubiquitin-like modifier FAT10 stimulates the activity of the deubiquitylating enzyme OTUB1

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BIALAS, Johanna, Annika N. BÖHM, Nicola CATONE, Annette AICHEM, Marcus GROETTRUP, 2019. The ubiquitin-like modifier FAT10 stimulates the activity of the deubiquitylating enzyme OTUB1. In: The Journal of Biological Chemistry : JBC. 294(12), pp. 4315-4330. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.RA118.005406

@article{Bialas2019-03-22ubiqu-45089, title={The ubiquitin-like modifier FAT10 stimulates the activity of the deubiquitylating enzyme OTUB1}, year={2019}, doi={10.1074/jbc.RA118.005406}, number={12}, volume={294}, issn={0021-9258}, journal={The Journal of Biological Chemistry : JBC}, pages={4315--4330}, author={Bialas, Johanna and Böhm, Annika N. and Catone, Nicola and Aichem, Annette and Groettrup, Marcus} }

<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/123456789/45089"> <dc:language>eng</dc:language> <dc:creator>Groettrup, Marcus</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-02-19T10:39:38Z</dcterms:available> <dc:creator>Bialas, Johanna</dc:creator> <dcterms:rights rdf:resource="https://kops.uni-konstanz.de/page/termsofuse"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Groettrup, Marcus</dc:contributor> <dcterms:issued>2019-03-22</dcterms:issued> <dc:contributor>Bialas, Johanna</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dc:creator>Catone, Nicola</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/45089"/> <dc:contributor>Böhm, Annika N.</dc:contributor> <dcterms:abstract xml:lang="eng">The deubiquitylation of target proteins is mediated by DUBs such as OTUB1 which plays an important role in the immune response, cell cycle progression and DNA repair. Within these processes OTUB1 reduces the ubiquitylation of target proteins in two distinct ways, either by using its catalytic DUB activity or in a non-catalytic manner by inhibiting the E2 conjugating enzyme. Here, we show that the ubiquitin-like modifier FAT10 is regulating the OTUB1 stability and functionality in different manners. Covalent FAT10ylation of OTUB1 results in its proteasomal degradation whereas a non-covalent interaction stabilizes OTUB1. We provide evidence that OTUB1 directly interacts with FAT10 and the E2 conjugating enzyme USE1. This interaction strongly stimulates the OTUB1 DUB activity towards K48-linked diubiquitin. Furthermore, the non-covalent interaction between FAT10 and OTUB1 not only enhances its isopeptidase activity towards K48-linked ubiquitin moieties but also strengthens its non-catalytic activity in reducing K63 polyubiquitylation of its target protein TRAF3. Additionally, the cellular clearance of overall polyubiquitylation by OTUB1 was strongly stimulated through the presence of FAT10. Addition of FAT10 also led to an increased interaction between OTUB1 and its cognate E2 UbcH5B implying a function of FAT10 in the inhibition of polyubiquitylation. Overall, these data indicate that FAT10 does not only play a role in covalent modification and leading its substrates to proteasomal degradation, but that it also regulates stability and functionality of target proteins by interacting in a non-covalent manner. Thereby FAT10 is able to exert a major influence on ubiquitylation processes.</dcterms:abstract> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Aichem, Annette</dc:creator> <dc:contributor>Aichem, Annette</dc:contributor> <dc:creator>Böhm, Annika N.</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Catone, Nicola</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-02-19T10:39:38Z</dc:date> <dcterms:title>The ubiquitin-like modifier FAT10 stimulates the activity of the deubiquitylating enzyme OTUB1</dcterms:title> </rdf:Description> </rdf:RDF>

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