Enzymatic blockade of the ubiquitin-proteasome pathway
Abstract: Ubiquitin-dependent processes control much of cellular physiology. We show that expression of a highly active, Epstein-Barr virus-derived deubiquitylating enzyme (EBV-DUB) blocks proteasomal degradation of cytosolic and ER-derived proteins by preemptive removal of ubiquitin from proteasome substrates, a treatment less toxic than the use of proteasome inhibitors. Recognition of misfolded proteins in the ER lumen, their dislocation to the cytosol, and degradation are usually tightly coupled but can be uncoupled by the EBV-DUB: a misfolded glycoprotein that originates in the ER accumulates in association with cytosolic chaperones as a deglycosylated intermediate. Our data underscore the necessity of a DUB activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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PLoS biology. - 8, 3 (2011) , e1000605, ISSN: 1545-7885
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2019
- Creator
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Ernst, Robert
Claessen, Jasper H. L.
Mueller, Britta
Sanyal, Sumana
Spooner, Eric
Veen, Annemarthe G. van der
Kirak, Oktay
Schlieker, Christian
Weihofen, Wilhelm
Ploegh, Hidde L.
- DOI
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10.1371/journal.pbio.1000605
- URN
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urn:nbn:de:bsz:25-freidok-1506752
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:48 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Ernst, Robert
- Claessen, Jasper H. L.
- Mueller, Britta
- Sanyal, Sumana
- Spooner, Eric
- Veen, Annemarthe G. van der
- Kirak, Oktay
- Schlieker, Christian
- Weihofen, Wilhelm
- Ploegh, Hidde L.
- Universität
Time of origin
- 2019
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Metabolic Regulation of the Ubiquitin-Proteasome System
The Ubiquitin−Proteasome System in Immune Cells
Thermal adaptation of the ubiquitin-proteasome system
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The Ubiquitin−Proteasome System in Immune Cells
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Polypharmacology of small molecules targeting the ubiquitin-proteasome and ubiquitin-like systems
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