How an inhibitor of the HIV-I protease modulates proteasome activity

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
1999
Autor:innen
Holzhütter, Hermann-Georg
Bogyo, Matthew
Kairies, Norman
Groll, Michael
Giuli, Rita de
Emch, Sabine
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Journal of Biological Chemistry. 1999, 274(50), pp. 35734-35740. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.274.50.35734
Zusammenfassung

The human immunodeficiency virus, type I protease inhibitor Ritonavir has been used successfully in AIDS therapy for 4 years. Clinical observations suggested that Ritonavir may exert a direct effect on the immune system unrelated to inhibition of the human immunodeficiency virus, type I protease. In fact, Ritonavir inhibited the major histocompatibility complex class I restricted presentation of several viral antigens at therapeutically relevant concentrations (5 microM). In search of a molecular target we found that Ritonavir inhibited the chymotrypsin-like activity of the proteasome whereas the tryptic activity was enhanced. In this study we kinetically analyzed how Ritonavir modulates proteasome activity and what consequences this has on cellular functions of the proteasome. Ritonavir is a reversible effector of proteasome activity that protected the subunits MB-1 (X) and/or LMP7 from covalent active site modification with the vinyl sulfone inhibitor(125)I-NLVS, suggesting that they are the prime targets for competitive inhibition by Ritonavir. At low concentrations of Ritonavir (5 microM) cells were more sensitive to canavanine but proliferated normally whereas at higher concentrations (50 microM) protein degradation was affected, and the cell cycle was arrested in the G(1)/S phase. Ritonavir thus modulates antigen processing at concentrations at which vital cellular functions of the proteasome are not yet severely impeded. Proteasome modulators may hence qualify as therapeutics for the control of the cytotoxic immune response.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Datensätze
Zitieren
ISO 690SCHMIDTKE, Gunter, Hermann-Georg HOLZHÜTTER, Matthew BOGYO, Norman KAIRIES, Michael GROLL, Rita de GIULI, Sabine EMCH, Marcus GRÖTTRUP, 1999. How an inhibitor of the HIV-I protease modulates proteasome activity. In: Journal of Biological Chemistry. 1999, 274(50), pp. 35734-35740. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.274.50.35734
BibTex
@article{Schmidtke1999inhib-22236,
  year={1999},
  doi={10.1074/jbc.274.50.35734},
  title={How an inhibitor of the HIV-I protease modulates proteasome activity},
  number={50},
  volume={274},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={35734--35740},
  author={Schmidtke, Gunter and Holzhütter, Hermann-Georg and Bogyo, Matthew and Kairies, Norman and Groll, Michael and Giuli, Rita de and Emch, Sabine 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/123456789/22236">
    <dc:creator>Holzhütter, Hermann-Georg</dc:creator>
    <dc:creator>Gröttrup, Marcus</dc:creator>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:contributor>Kairies, Norman</dc:contributor>
    <dc:creator>Emch, Sabine</dc:creator>
    <dc:contributor>Groll, Michael</dc:contributor>
    <dc:creator>Bogyo, Matthew</dc:creator>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Giuli, Rita de</dc:creator>
    <dcterms:issued>1999</dcterms:issued>
    <dc:contributor>Bogyo, Matthew</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Kairies, Norman</dc:creator>
    <dc:contributor>Emch, Sabine</dc:contributor>
    <dc:rights>terms-of-use</dc:rights>
    <dc:creator>Schmidtke, Gunter</dc:creator>
    <dcterms:abstract xml:lang="eng">The human immunodeficiency virus, type I protease inhibitor Ritonavir has been used successfully in AIDS therapy for 4 years. Clinical observations suggested that Ritonavir may exert a direct effect on the immune system unrelated to inhibition of the human immunodeficiency virus, type I protease. In fact, Ritonavir inhibited the major histocompatibility complex class I restricted presentation of several viral antigens at therapeutically relevant concentrations (5 microM). In search of a molecular target we found that Ritonavir inhibited the chymotrypsin-like activity of the proteasome whereas the tryptic activity was enhanced. In this study we kinetically analyzed how Ritonavir modulates proteasome activity and what consequences this has on cellular functions of the proteasome. Ritonavir is a reversible effector of proteasome activity that protected the subunits MB-1 (X) and/or LMP7 from covalent active site modification with the vinyl sulfone inhibitor(125)I-NLVS, suggesting that they are the prime targets for competitive inhibition by Ritonavir. At low concentrations of Ritonavir (5 microM) cells were more sensitive to canavanine but proliferated normally whereas at higher concentrations (50 microM) protein degradation was affected, and the cell cycle was arrested in the G(1)/S phase. Ritonavir thus modulates antigen processing at concentrations at which vital cellular functions of the proteasome are not yet severely impeded. Proteasome modulators may hence qualify as therapeutics for the control of the cytotoxic immune response.</dcterms:abstract>
    <dc:contributor>Schmidtke, Gunter</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-03-01T10:45:06Z</dc:date>
    <dcterms:title>How an inhibitor of the HIV-I protease modulates proteasome activity</dcterms:title>
    <dc:contributor>Gröttrup, Marcus</dc:contributor>
    <dc:contributor>Giuli, Rita de</dc:contributor>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/22236"/>
    <dc:creator>Groll, Michael</dc:creator>
    <dcterms:bibliographicCitation>The journal of biological chemistry : JBC ; 274 (1999), 50. - S. 35734-35740</dcterms:bibliographicCitation>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-03-01T10:45:06Z</dcterms:available>
    <dc:contributor>Holzhütter, Hermann-Georg</dc:contributor>
    <dc:language>eng</dc:language>
  </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
Diese Publikation teilen