Affiliation:
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.
Funder
Gordon and Betty Moore Foundation
National Institutes of Health
Boehringer Ingelheim Fonds
V Foundation for Cancer Research
Sidney Kimmel Foundation for Cancer Research
Camille and Henry Dreyfus Foundation
Howard Hughes Medical Institute
Beckman Institute, California Institute of Technology
Heritage Research Institute
Edward Mallinckrodt, Jr. Foundation
Donald E. and Delia B. Baxter Foundation
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Cited by
144 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献