Jump to ContentJump to Main Navigation
Show Summary Details
More options …

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

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 380, Issue 6 (Jun 1999)

Issues

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

Abstract

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.

Export Citation

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

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Anthony M. Esposito and Terri Goss Kinzy
Journal of Biological Chemistry, 2010, Volume 285, Number 49, Page 37995
[2]
Ying Wu, Daniel J. Termine, Matthew T. Swulius, Kelley W. Moremen, and Richard N. Sifers
Journal of Biological Chemistry, 2007, Volume 282, Number 7, Page 4841
[3]
Roberta Mancini, Markus Aebi, and Ari Helenius
Journal of Biological Chemistry, 2003, Volume 278, Number 47, Page 46895
[4]
Alexander W. Bell, Malcolm A. Ward, Walter P. Blackstock, Hamzah N. M. Freeman, Jyoti S. Choudhary, Alan P. Lewis, Dipti Chotai, Ali Fazel, Jennifer N. Gushue, Jacques Paiement, Sandrine Palcy, Eric Chevet, Myriam Lafrenière-Roula, Roberto Solari, David Y. Thomas, Adele Rowley, and John J. M. Bergeron
Journal of Biological Chemistry, 2001, Volume 276, Number 7, Page 5152
[5]
A.V. Morozov, D.S. Spasskaya, D.S. Karpov, and V.L. Karpov
FEBS Letters, 2014, Volume 588, Number 20, Page 3713
[7]
Federica Brandizzi, Sally Hanton, Luis L. Pinto daSilva, Petra Boevink, David Evans, Karl Oparka, Jurgen Denecke, and Chris Hawes
The Plant Journal, 2003, Volume 34, Number 3, Page 269

Comments (0)

Please log in or register to comment.
Log in