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Elife. 2016 Aug 23;5. pii: e19105. doi: 10.7554/eLife.19105.

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

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
2
Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institue, California Institute of Technology, Pasadena, United States.
3
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, United States.
4
Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.

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.

KEYWORDS:

S. cerevisiae; biochemistry; cell biology; human; protein quality control; ribosomal protein; ubiquitin-proteasome system

PMID:
27552055
PMCID:
PMC5026473
DOI:
10.7554/eLife.19105
[Indexed for MEDLINE]
Free PMC Article

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