Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol

Lade...
Vorschaubild
Dateien
Hellwig_2-1gawqolj6cn3e7pdf.pdf
Hellwig_2-1gawqolj6cn3e7pdf.pdfGröße: 2.78 MBDownloads: 72
Datum
2022
Autor:innen
Hellwig, Christian T.
Skoko, Josip
Dyck, Lydia
Hanna, Carol
Wentges, Alexa
Langlais, Claudia
Hagenlocher, Cathrin
Mack, Alexandra
Rehm, Markus
et al.
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Hybrid
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Cell Death and Differentiation. Nature Publishing Group. 2022, 29(1), pp. 147-155. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/s41418-021-00843-7
Zusammenfassung

Cancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690HELLWIG, Christian T., M. Eugenia DELGADO, Josip SKOKO, Lydia DYCK, Carol HANNA, Alexa WENTGES, Claudia LANGLAIS, Cathrin HAGENLOCHER, Alexandra MACK, Markus REHM, 2022. Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol. In: Cell Death and Differentiation. Nature Publishing Group. 2022, 29(1), pp. 147-155. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/s41418-021-00843-7
BibTex
@article{Hellwig2022-01Prote-54739,
  year={2022},
  doi={10.1038/s41418-021-00843-7},
  title={Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol},
  number={1},
  volume={29},
  issn={1350-9047},
  journal={Cell Death and Differentiation},
  pages={147--155},
  author={Hellwig, Christian T. and Delgado, M. Eugenia and Skoko, Josip and Dyck, Lydia and Hanna, Carol and Wentges, Alexa and Langlais, Claudia and Hagenlocher, Cathrin and Mack, Alexandra and Rehm, Markus}
}
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/123456789/54739">
    <dcterms:issued>2022-01</dcterms:issued>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/54739/1/Hellwig_2-1gawqolj6cn3e7pdf.pdf"/>
    <dc:language>eng</dc:language>
    <dc:contributor>Skoko, Josip</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-08-26T14:28:53Z</dc:date>
    <dc:creator>Skoko, Josip</dc:creator>
    <dc:contributor>Dyck, Lydia</dc:contributor>
    <dc:creator>Wentges, Alexa</dc:creator>
    <dc:creator>Dyck, Lydia</dc:creator>
    <dc:contributor>Wentges, Alexa</dc:contributor>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Hagenlocher, Cathrin</dc:creator>
    <dc:creator>Hanna, Carol</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Langlais, Claudia</dc:creator>
    <dc:creator>Hellwig, Christian T.</dc:creator>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:contributor>Hellwig, Christian T.</dc:contributor>
    <dc:contributor>Langlais, Claudia</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/54739"/>
    <dc:creator>Mack, Alexandra</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/54739/1/Hellwig_2-1gawqolj6cn3e7pdf.pdf"/>
    <dc:creator>Rehm, Markus</dc:creator>
    <dc:contributor>Mack, Alexandra</dc:contributor>
    <dcterms:title>Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol</dcterms:title>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Hanna, Carol</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-08-26T14:28:53Z</dcterms:available>
    <dc:contributor>Delgado, M. Eugenia</dc:contributor>
    <dcterms:abstract xml:lang="eng">Cancer cells that are resistant to Bax/Bak-dependent intrinsic apoptosis can be eliminated by proteasome inhibition. Here, we show that proteasome inhibition induces the formation of high molecular weight platforms in the cytosol that serve to activate caspase-8. The activation complexes contain Fas-associated death domain (FADD) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Furthermore, the complexes contain TRAIL-receptor 2 (TRAIL-R2) but not TRAIL-receptor 1 (TRAIL-R1). While RIPK1 inhibition or depletion did not affect proteasome inhibitor-induced cell death, TRAIL-R2 was found essential for efficient caspase-8 activation, since the loss of TRAIL-R2 expression abrogated caspase processing, significantly reduced cell death, and promoted cell re-growth after drug washout. Overall, our study provides novel insight into the mechanisms by which proteasome inhibition eliminates otherwise apoptosis-resistant cells, and highlights the crucial role of a ligand-independent but TRAIL-R2-dependent activation mechanism for caspase-8 in this scenario.</dcterms:abstract>
    <dc:creator>Delgado, M. Eugenia</dc:creator>
    <dc:contributor>Rehm, Markus</dc:contributor>
    <dc:contributor>Hagenlocher, Cathrin</dc:contributor>
  </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
Nein
Begutachtet
Ja
Diese Publikation teilen