The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation

Lade...
Vorschaubild
Dateien
Aichem_219921.pdf
Aichem_219921.pdfGröße: 1.23 MBDownloads: 315
Datum
2012
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
DOI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
EU-Projektnummer
DFG-Projektnummer
Projekt
Open Access-Veröffentlichung
Sammlungen
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
unikn.publication.listelement.citation.prefix.version.undefined
Journal of Cell Science. 2012, 125(19), pp. 4576-4585. ISSN 0021-9533. eISSN 1477-9137. Available under: doi: 10.1242/jcs.107789
Zusammenfassung

FAT10 is a ubiquitin-like modifier proposed to function in apoptosis induction, cell cycle control and NF-kB activation. Upon induction by pro-inflammatory cytokines, hundreds of endogenous substrates become covalently conjugated to FAT10 leading to their proteasomal degradation. Nevertheless, only three substrates have been identified so far to which FAT10 becomes covalently attached through a non-reducible isopeptide bond, and these are the FAT10-conjugating enzyme USE1 which auto-FAT10ylates itself in cis, the tumor suppressor p53 and the ubiquitin-activating enzyme UBE1 (UBA1). To identify additional FAT10 substrates and interaction partners, we used a new monoclonal FAT10-specific antibody to immunopurify endogenous FAT10 conjugates from interferon (IFN)cand tumor necrosis factor (TNF)alpha-stimulated cells for identification by mass spectrometry. In addition to two already known FAT10- interacting proteins, histone deacetylase 6 and UBA6, we identified 569 novel FAT10-interacting proteins involved in different functional pathways such as autophagy, cell cycle regulation, apoptosis and cancer. Thirty-one percent of all identified proteins were
categorized as putative covalently linked substrates. One of the identified proteins, the autophagosomal receptor p62/SQSTM1, was further investigated. p62 becomes covalently mono-FAT10ylated at several lysines, and FAT10 colocalizes with p62 in p62 bodies.
Strikingly, FAT10ylation of p62 leads to its proteasomal degradation, and prolonged induction of endogenous FAT10 expression by proinflammatory cytokines leads to a decrease of endogenous p62. The elucidation of the FAT10 degradome should enable a better understanding of why FAT10 has evolved as an additional transferable tag for proteasomal degradation.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Ubiquitin, Proteasome, FAT10, Proteomics, p62
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690AICHEM, Annette, Birte KALVERAM, Valentina SPINNENHIRN, Kathrin KLUGE, Nicola CATONE, Terje JOHANSEN, Marcus GRÖTTRUP, 2012. The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation. In: Journal of Cell Science. 2012, 125(19), pp. 4576-4585. ISSN 0021-9533. eISSN 1477-9137. Available under: doi: 10.1242/jcs.107789
BibTex
@article{Aichem2012-10-01prote-21992,
  year={2012},
  doi={10.1242/jcs.107789},
  title={The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation},
  number={19},
  volume={125},
  issn={0021-9533},
  journal={Journal of Cell Science},
  pages={4576--4585},
  author={Aichem, Annette and Kalveram, Birte and Spinnenhirn, Valentina and Kluge, Kathrin and Catone, Nicola and Johansen, Terje and Gröttrup, Marcus}
}
RDF
<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/server/rdf/resource/123456789/21992">
    <dc:creator>Aichem, Annette</dc:creator>
    <dcterms:bibliographicCitation>Journal of Cell Science ; 125 (2012), 19. - S. 4576-4585</dcterms:bibliographicCitation>
    <dc:contributor>Kalveram, Birte</dc:contributor>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21992/2/Aichem_219921.pdf"/>
    <dc:creator>Gröttrup, Marcus</dc:creator>
    <dcterms:issued>2012-10-01</dcterms:issued>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-03-01T14:02:21Z</dcterms:available>
    <dc:contributor>Aichem, Annette</dc:contributor>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/21992"/>
    <dc:contributor>Catone, Nicola</dc:contributor>
    <dc:contributor>Johansen, Terje</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/21992/2/Aichem_219921.pdf"/>
    <dcterms:abstract xml:lang="eng">FAT10 is a ubiquitin-like modifier proposed to function in apoptosis induction, cell cycle control and NF-kB activation. Upon induction by pro-inflammatory cytokines, hundreds of endogenous substrates become covalently conjugated to FAT10 leading to their proteasomal degradation. Nevertheless, only three substrates have been identified so far to which FAT10 becomes covalently attached through a non-reducible isopeptide bond, and these are the FAT10-conjugating enzyme USE1 which auto-FAT10ylates itself in cis, the tumor suppressor p53 and the ubiquitin-activating enzyme UBE1 (UBA1). To identify additional FAT10 substrates and interaction partners, we used a new monoclonal FAT10-specific antibody to immunopurify endogenous FAT10 conjugates from interferon (IFN)cand tumor necrosis factor (TNF)alpha-stimulated cells for identification by mass spectrometry. In addition to two already known FAT10- interacting proteins, histone deacetylase 6 and UBA6, we identified 569 novel FAT10-interacting proteins involved in different functional pathways such as autophagy, cell cycle regulation, apoptosis and cancer. Thirty-one percent of all identified proteins were&lt;br /&gt;categorized as putative covalently linked substrates. One of the identified proteins, the autophagosomal receptor p62/SQSTM1, was further investigated. p62 becomes covalently mono-FAT10ylated at several lysines, and FAT10 colocalizes with p62 in p62 bodies.&lt;br /&gt;Strikingly, FAT10ylation of p62 leads to its proteasomal degradation, and prolonged induction of endogenous FAT10 expression by proinflammatory cytokines leads to a decrease of endogenous p62. The elucidation of the FAT10 degradome should enable a better understanding of why FAT10 has evolved as an additional transferable tag for proteasomal degradation.</dcterms:abstract>
    <dc:language>eng</dc:language>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:rights>terms-of-use</dc:rights>
    <dc:creator>Spinnenhirn, Valentina</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:contributor>Spinnenhirn, Valentina</dc:contributor>
    <dc:creator>Johansen, Terje</dc:creator>
    <dcterms:title>The proteomic analysis of endogenous FAT10 substrates identifies p62/SQSTM1 as a substrate of FAT10ylation</dcterms:title>
    <dc:contributor>Kluge, Kathrin</dc:contributor>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Catone, Nicola</dc:creator>
    <dc:creator>Kluge, Kathrin</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-03-01T14:02:21Z</dc:date>
    <dc:creator>Kalveram, Birte</dc:creator>
    <dc:contributor>Gröttrup, Marcus</dc:contributor>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet