A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins
Abstract
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.
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Funding
Gordon and Betty Moore Foundation (GBMF775)
- Tanya R Porras-Yakushi
- Michael J Sweredoski
- Sonja Hess
Edward Mallinckrodt (Scholar Award)
- André Hoelz
Donald E. and Delia B. Baxter Foundation
- Min-Kyung Sung
National Institutes of Health (1S10RR029594)
- Sonja Hess
National Institutes of Health (F32GM112308)
- Justin M Reitsma
Boehringer Ingelheim Fonds
- Ferdinand M Huber
V Foundation for Cancer Research (Albert Wyrick V Scholar Award)
- André Hoelz
Sidney Kimmel Foundation for Cancer Research (Scholar Award)
- André Hoelz
Camille and Henry Dreyfus Foundation (Teacher-Scholar Award)
- André Hoelz
Howard Hughes Medical Institute
- Raymond J Deshaies
Beckman Institute, California Institute of Technology
- Tanya R Porras-Yakushi
- Michael J Sweredoski
- Sonja Hess
Heritage Research Institute
- André Hoelz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 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.
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