Publikation:

FAT10 and NUB1L cooperate to activate the 26S proteasome

Lade...
Vorschaubild

Dateien

Brockmann_2-vdli3fw5fz7z2.pdf
Brockmann_2-vdli3fw5fz7z2.pdfGröße: 3.11 MBDownloads: 6

Datum

2023

Autor:innen

Brockmann, Florian

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

DOI (zitierfähiger Link)
ArXiv-ID

Internationale Patentnummer

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Open Access Green
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Dissertation
Publikationsstatus
Published

Erschienen in

Zusammenfassung

The homeostasis of proteins including protein synthesis, proper folding, post-translational modifications (PTM) as well as recycling and degradation of proteins is an essential aspect of cellular life. The proteasome plays a key role by degrading short-lived, misfolded, and damaged proteins within cells. It is known that the ATP-dependent degradation of intracellular proteins is caused by the 76-amino acid polypeptide ubiquitin. Another PTM, fatylation, means covalent attachment of the ubiquitin like protein FAT10 (HLA-F adjacent transcript 10), serves in a similar way and guides labeled proteins are degraded by the proteasome. The interaction of the 19S regulatory particle of the 26S proteasome with ubiquitylated proteins leads to gate opening of the 20S core particle and increases its proteolytic activity by displacing the inhibitory deubiquitylation enzyme USP14 from the 19S regulator subunit RPN1. Covalent modification with the cytokine inducible ubiquitin-like modifier FAT10 is an alternative signal for proteasomal degradation. In this thesis, it is shown that FAT10 and its interaction partner NUB1L facilitate the gate opening of the 20S proteasome in a ubiquitin- and USP14-independent manner. It is also demonstrated, that monomeric FAT10 is capable to activate all peptidolytic activities of the 26S proteasome exclusively in interplay with NUB1L by binding to the UBA-domains of NUB1L and thereby interfering with NUB1L dimerization. The binding of FAT10 to NUB1L increases the affinity of NUB1L for the subunit RPN1. In conclusion, the herein described cooperation of FAT10 and NUB1L is a substrate-induced mechanism to activate the 26S proteasome.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690BROCKMANN, Florian, 2023. FAT10 and NUB1L cooperate to activate the 26S proteasome [Dissertation]. Konstanz: Universität Konstanz
BibTex
@phdthesis{Brockmann2023FAT10-72086,
  title={FAT10 and NUB1L cooperate to activate the 26S proteasome},
  year={2023},
  author={Brockmann, Florian},
  address={Konstanz},
  school={Universität Konstanz}
}
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/123456789/72086">
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-29T07:47:47Z</dc:date>
    <dc:creator>Brockmann, Florian</dc:creator>
    <dcterms:title>FAT10 and NUB1L cooperate to activate the 26S proteasome</dcterms:title>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:issued>2023</dcterms:issued>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/72086"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-29T07:47:47Z</dcterms:available>
    <dcterms:abstract>The homeostasis of proteins including protein synthesis, proper folding, post-translational modifications (PTM) as well as recycling and degradation of proteins is an essential aspect of cellular life. The proteasome plays a key role by degrading short-lived, misfolded, and damaged proteins within cells. It is known that the ATP-dependent degradation of intracellular proteins is caused by the 76-amino acid polypeptide ubiquitin. Another PTM, fatylation, means covalent attachment of the ubiquitin like protein FAT10 (HLA-F adjacent transcript 10), serves in a similar way and guides labeled proteins are degraded by the proteasome.
The interaction of the 19S regulatory particle of the 26S proteasome with ubiquitylated proteins leads to gate opening of the 20S core particle and increases its proteolytic activity by displacing the inhibitory deubiquitylation enzyme USP14 from the 19S regulator subunit RPN1. Covalent modification with the cytokine inducible ubiquitin-like modifier FAT10 is an alternative signal for proteasomal degradation. In this thesis, it is shown that FAT10 and its interaction partner NUB1L facilitate the gate opening of the 20S proteasome in a ubiquitin- and USP14-independent manner. It is also demonstrated, that monomeric FAT10 is capable to activate all peptidolytic activities of the 26S proteasome exclusively in interplay with NUB1L by binding to the UBA-domains of NUB1L and thereby interfering with NUB1L dimerization. The binding of FAT10 to NUB1L increases the affinity of NUB1L for the subunit RPN1. In conclusion, the herein described cooperation of FAT10 and NUB1L is a substrate-induced mechanism to activate the 26S proteasome.</dcterms:abstract>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/72086/4/Brockmann_2-vdli3fw5fz7z2.pdf"/>
    <dc:rights>terms-of-use</dc:rights>
    <dc:language>eng</dc:language>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Brockmann, Florian</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/72086/4/Brockmann_2-vdli3fw5fz7z2.pdf"/>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
  </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

June 21, 2023
Hochschulschriftenvermerk
Konstanz, Univ., Diss., 2023
Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Begutachtet
Diese Publikation teilen