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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
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Volume 380, Issue 6 (Jun 1999)


Cycloheximide, a New Tool to Dissect Specific Steps in ER-Associated Degradation of Different Substrates

C. Amshoff / H.-M. Jäck / I.G. Haas
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.1999.083


To study the degradation requirements of unassembled immunoglobulin (Ig) chains, we heterologously expressed a cDNA encoding the secretory form of murine μ in the yeast S. cerevisiae. We found that μ chains were translocated into and retained in the endoplasmic reticulum (ER) as they were N-glycosylated and bound to the yeast homolog of BiP, Kar2p. Similar to mutant yeast carboxypeptidase Y (CPY*), known to undergo cytosolic degradation, μ protein is stabilized in yeast mutants lacking the ubiquitinating enzymes Ubc6p and Ubc7p or in cells overexpressing mutant ubiquitin. Unexpectedly, the translation inhibitor cycloheximide (CHX), but not puromycin, led to the accumulation of polyubiquitinated μ chains that were still glycosylated. By contrast, degradation of CPY* was not impaired by CHX, indicating that the drug affects a substrate-specific degradation step. In contrast to the situation for CPY*, the ER-transmembrane protein Der1p is not essential for μ degradation. Strikingly, however, the CHX-induced accumulation of polyubiquitinated Igμ chains was stronger in ∆der1-mutants as compared to wild-type cells, indicating an additive effect of two inhibitory conditions. The results support a previously unknown activity of CHX, i.e. impairing the degradation of transport-incompetent secretory μ chains. Moreover, this activity will allow to dissect substrate-specific steps in ER associated protein degradation.

About the article

Published Online: 2005-06-01

Published in Print: 1999-06-01

Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.1999.083.

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Copyright © 1999 by Walter de Gruyter GmbH & Co. KG. Copyright Clearance Center

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