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A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins

Sung, Min-Kyung and Porras-Yakushi, Tanya R. and Reitsma, Justin M. and Huber, Ferdinand M. and Sweredoski, Michael J. and Hoelz, André and Hess, Sonja and Deshaies, Raymond J. (2016) A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins. eLife, 5 . Art. No. e19105. ISSN 2050-084X. PMCID PMC5026473.

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Overproduced yeast ribosomal protein (RP) Rpl26 fails to assemble into ribosomes and is degraded in the nucleus/nucleolus by a ubiquitin-proteasome system quality control pathway comprising the E2 enzymes Ubc4/Ubc5 and the ubiquitin ligase Tom1. tom1 cells show reduced ubiquitination of multiple RPs, exceptional accumulation of detergent-insoluble proteins including multiple RPs, and hypersensitivity to imbalances in production of RPs and rRNA, indicative of a profound perturbation to proteostasis. Tom1 directly ubiquitinates unassembled RPs primarily via residues that are concealed in mature ribosomes. Together, these data point to an important role for Tom1 in normal physiology and prompt us to refer to this pathway as ERISQ, for excess ribosomal protein quality control. A similar pathway, mediated by the Tom1 homolog Huwe1, restricts accumulation of overexpressed hRpl26 in human cells. We propose that ERISQ is a key element of the quality control machinery that sustains protein homeostasis and cellular fitness in eukaryotes.

Item Type:Article
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URLURL TypeDescription CentralArticle
Sweredoski, Michael J.0000-0003-0878-3831
Hoelz, André0000-0003-1726-0127
Hess, Sonja0000-0002-5904-9816
Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2016, Sung et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received June 25, 2016. Accepted August 19, 2016. Published August 23, 2016. We are grateful to members of the Deshaies laboratory for helpful advice and Rati Verma for critical reading of this manuscript. We thank Jonathan Warner, Christine Guthrie, Sarah Luchansky, Ling Song, Won-Ki Huh, George Moldovan, and Helle Ulrich for generously providing reagents and helpful discussions. We also thank Thang Nguyen and Rati Verma for numerous helpful suggestions regarding biochemical experiments. We thank Annie Moradian and Roxana Eggleston-Rangel for mass spectrometric assistance. RJD is an Investigator of the HHMI. Funding: Gordon and Betty Moore Foundation; GBMF775. National Institutes of Health; F32GM112308. Boehringer Ingelheim Fonds. V Foundation for Cancer Research; Albert Wyrick V Scholar Award. Sidney Kimmel Foundation for Cancer Research; Scholar Award. Camille and Henry Dreyfus Foundation; Teacher-Scholar Award. Howard Hughes Medical Institute. Beckman Institute, California Institute of Technology. Heritage Research Institute. Edward Mallinckrodt, Jr. Foundation; Scholar Award. Donald E. and Delia B. Baxter Foundation. National Institutes of Health; 1S10RR029594. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Competing interests: RJD: Reviewing Editor, eLife. The other authors declare that no competing interests exist.
Funding AgencyGrant Number
Gordon and Betty Moore FoundationGBMF775
Boehringer Ingelheim FondsUNSPECIFIED
V Foundation for Cancer ResearchUNSPECIFIED
Sidney Kimmel Foundation for Cancer ResearchUNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Edward Mallinckrodt, Jr. FoundationUNSPECIFIED
Donald E. and Delia B. Baxter FoundationUNSPECIFIED
PubMed Central ID:PMC5026473
Record Number:CaltechAUTHORS:20160901-122707403
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Official Citation:A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins Min-Kyung Sung Tanya R Porras-Yakushi Justin M Reitsma Ferdinand M Huber Michael J Sweredoski André Hoelz Sonja Hess Raymond J Deshaies eLife 2016;10.7554/eLife.19105
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:70122
Deposited By: Tony Diaz
Deposited On:01 Sep 2016 19:56
Last Modified:03 Oct 2019 10:28

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