Publikation: Phosphorylated FAT10 Is More Efficiently Conjugated to Substrates, Does Not Bind to NUB1L, and Does Not Alter Degradation by the Proteasome
Dateien
Datum
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
Background: FAT10 is a member of the ubiquitin-like modifier family. Similar to ubiquitin, FAT10 has a distinct enzyme cascade consisting of E1-activating, E2-conjugating, and possibly several E3-ligating enzymes, which will covalently link FAT10 to substrate proteins in order to target them directly for proteasomal degradation. FAT10 was reported to be phosphorylated by IKKβ during infection with influenza A virus.
Methods: To assess the difference between the FAT10-dependent degradation of phosphorylated FAT10 and the non-phosphorylated FAT10 wild type (FAT10 WT), a mutated FAT10 that mimicked phosphorylation (FAT10 D) was constructed by replacing several serine residues and one threonine residue with aspartic or glutamic acid. The FAT10 degradation or conjugation was compared between the phospho-mimetic FAT10 and the wild-type FAT10 with respect to the dependence of the E3 ligase TRIM25, the UBL-UBA protein NUB1L, and the proteasomal ubiquitin receptor RPN10.
Results: The phospho-mimetic FAT10 was more efficiently conjugated to substrate proteins as compared to the wild-type FAT10, particularly if TRIM25 was co-expressed. Additionally, the phospho-mimetic FAT10 was not bound by NUB1L. However, this did not affect FAT10 D or FAT10 WT degradation. No differences were found in the binding affinity of phospho-mimetic FAT10 to RPN10.
Conclusions: In brief, the phospho-mimetic FAT10 shows enhanced conjugation efficiency, but phosphorylation does not alter its degradation by the proteasome. This reveals that phosphorylation may fine-tune FAT10’s interactions with specific interaction partners without disrupting its core function of proteasomal degradation.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
CAO, Jinjing, Annette AICHEM, Michael BASLER, Gerardo Omar ALVAREZ SALINAS, Gunter SCHMIDTKE, 2024. Phosphorylated FAT10 Is More Efficiently Conjugated to Substrates, Does Not Bind to NUB1L, and Does Not Alter Degradation by the Proteasome. In: Biomedicines. MDPI. 2024, 12(12), 2795. eISSN 2227-9059. Verfügbar unter: doi: 10.3390/biomedicines12122795BibTex
@article{Cao2024-12-09Phosp-71883, year={2024}, doi={10.3390/biomedicines12122795}, title={Phosphorylated FAT10 Is More Efficiently Conjugated to Substrates, Does Not Bind to NUB1L, and Does Not Alter Degradation by the Proteasome}, number={12}, volume={12}, journal={Biomedicines}, author={Cao, Jinjing and Aichem, Annette and Basler, Michael and Alvarez Salinas, Gerardo Omar and Schmidtke, Gunter}, note={Article Number: 2795} }
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/123456789/71883"> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/71883"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dc:contributor>Basler, Michael</dc:contributor> <dc:contributor>Cao, Jinjing</dc:contributor> <dc:creator>Cao, Jinjing</dc:creator> <dcterms:abstract>Background: FAT10 is a member of the ubiquitin-like modifier family. Similar to ubiquitin, FAT10 has a distinct enzyme cascade consisting of E1-activating, E2-conjugating, and possibly several E3-ligating enzymes, which will covalently link FAT10 to substrate proteins in order to target them directly for proteasomal degradation. FAT10 was reported to be phosphorylated by IKKβ during infection with influenza A virus. Methods: To assess the difference between the FAT10-dependent degradation of phosphorylated FAT10 and the non-phosphorylated FAT10 wild type (FAT10 WT), a mutated FAT10 that mimicked phosphorylation (FAT10 D) was constructed by replacing several serine residues and one threonine residue with aspartic or glutamic acid. The FAT10 degradation or conjugation was compared between the phospho-mimetic FAT10 and the wild-type FAT10 with respect to the dependence of the E3 ligase TRIM25, the UBL-UBA protein NUB1L, and the proteasomal ubiquitin receptor RPN10. Results: The phospho-mimetic FAT10 was more efficiently conjugated to substrate proteins as compared to the wild-type FAT10, particularly if TRIM25 was co-expressed. Additionally, the phospho-mimetic FAT10 was not bound by NUB1L. However, this did not affect FAT10 D or FAT10 WT degradation. No differences were found in the binding affinity of phospho-mimetic FAT10 to RPN10. Conclusions: In brief, the phospho-mimetic FAT10 shows enhanced conjugation efficiency, but phosphorylation does not alter its degradation by the proteasome. This reveals that phosphorylation may fine-tune FAT10’s interactions with specific interaction partners without disrupting its core function of proteasomal degradation.</dcterms:abstract> <dc:language>eng</dc:language> <dc:contributor>Aichem, Annette</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dc:contributor>Schmidtke, Gunter</dc:contributor> <dc:creator>Basler, Michael</dc:creator> <dc:creator>Alvarez Salinas, Gerardo Omar</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-15T08:03:06Z</dcterms:available> <dc:creator>Schmidtke, Gunter</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/71883/4/Cao_2-chrf7wxjiumo8.pdf"/> <dc:contributor>Alvarez Salinas, Gerardo Omar</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-15T08:03:06Z</dc:date> <dc:rights>Attribution 4.0 International</dc:rights> <dcterms:title>Phosphorylated FAT10 Is More Efficiently Conjugated to Substrates, Does Not Bind to NUB1L, and Does Not Alter Degradation by the Proteasome</dcterms:title> <dc:creator>Aichem, Annette</dc:creator> <dcterms:issued>2024-12-09</dcterms:issued> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/71883/4/Cao_2-chrf7wxjiumo8.pdf"/> </rdf:Description> </rdf:RDF>