Genetic analysis reveals functions of atypical polyubiquitin chains
- University of California, San Francisco, United States
- Amgen Research, United States
- Lawrence Berkeley National Laboratory, United States
- Stanford University, United States
- University of California San Francisco, United States
Abstract
Although polyubiquitin chains linked through all lysines of ubiquitin exist, specific functions are well-established only for lysine-48 and lysine-63 linkages in Saccharomyces cerevisiae. To uncover pathways regulated by distinct linkages, genetic interactions between a gene deletion library and a panel of lysine-to-arginine ubiquitin mutants were systematically identified. The K11R mutant had strong genetic interactions with threonine biosynthetic genes. Consistently, we found that K11R mutants import threonine poorly. The K11R mutant also exhibited a strong genetic interaction with a subunit of the anaphase-promoting complex (APC), suggesting a role in cell cycle regulation. K11-linkages are important for vertebrate APC function, but this was not previously described in yeast. We show that the yeast APC also modifies substrates with K11-linkages in vitro, and that those chains contribute to normal APC-substrate turnover in vivo. This study reveals comprehensive genetic interactomes of polyubiquitin chains and characterizes the role of K11-chains in two biological pathways.
Data availability
All datasets generated are included as Supplementary Files 4 (SGA dataset) and 5 (quantitative proteomics).
Article and author information
Author details
Fernando Meza Gutierrez
Funding
National Institutes of Health (R35 GM118104)
- David P Toczyski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michael Rape, University of California, Berkeley, United States
Version history
- Received: October 18, 2018
- Accepted: November 30, 2018
- Accepted Manuscript published: December 14, 2018 (version 1)
- Version of Record published: December 24, 2018 (version 2)
Copyright
© 2018, Meza Gutierrez 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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Genetic analysis reveals functions of atypical polyubiquitin chains
eLife 7:e42955.
https://doi.org/10.7554/eLife.42955
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