Enzymatic Blockade of the Ubiquitin-Proteasome Pathway
Name
Ernst-2011-Enzymatic Blockade o.pdf
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1.42 MB
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Checksum (MD5)
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Author(s)
Ernst, Robert
Claessen, Jasper H. L.
Mueller, Britta
Sanyal, Sumana
Spooner, Eric
van der Veen, Annemarthe G.
Kirak, Oktay
Schlieker, Christian D.
Weihofen, Wilhelm A.
Ploegh, Hidde
Date Issued
March 2011
Journal
PLoS Biology
Publisher
Public Library of Science
Citation
Ernst, Robert et al. “Enzymatic Blockade of the Ubiquitin-Proteasome Pathway.” Ed. Jonathan D. Ashwell. PLoS Biology 8.3 (2011) : e1000605.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1371/journal.pbio.1000605
