1. Biochemistry and Chemical Biology
  2. Cell Biology
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A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins

Research Article
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Cite this article as: eLife 2016;5:e19105 doi: 10.7554/eLife.19105

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.

Article and author information

Author details

  1. Min-Kyung Sung

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0513-6834
  2. Tanya R Porras-Yakushi

    Proteome Exploration Laboratory, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  3. Justin M Reitsma

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  4. Ferdinand M Huber

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  5. Michael J Sweredoski

    Proteome Exploration Laboratory, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  6. André Hoelz

    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  7. Sonja Hess

    Proteome Exploration Laboratory, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  8. Raymond J Deshaies

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    deshaies@caltech.edu
    Competing interests
    Raymond J Deshaies, Reviewing Editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3671-9354

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.

Reviewing Editor

  1. Wade Harper, Harvard Medical School, United States

Publication history

  1. Received: June 25, 2016
  2. Accepted: August 19, 2016
  3. Accepted Manuscript published: August 23, 2016 (version 1)
  4. Version of Record published: September 16, 2016 (version 2)

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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