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Genetic analysis reveals functions of atypical polyubiquitin chains
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 p...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305200/ https://www.ncbi.nlm.nih.gov/pubmed/30547882 http://dx.doi.org/10.7554/eLife.42955 |
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author | Meza Gutierrez, Fernando Simsek, Deniz Mizrak, Arda Deutschbauer, Adam Braberg, Hannes Johnson, Jeffrey Xu, Jiewei Shales, Michael Nguyen, Michelle Tamse-Kuehn, Raquel Palm, Curt Steinmetz, Lars M Krogan, Nevan J Toczyski, David P |
author_facet | Meza Gutierrez, Fernando Simsek, Deniz Mizrak, Arda Deutschbauer, Adam Braberg, Hannes Johnson, Jeffrey Xu, Jiewei Shales, Michael Nguyen, Michelle Tamse-Kuehn, Raquel Palm, Curt Steinmetz, Lars M Krogan, Nevan J Toczyski, David P |
author_sort | Meza Gutierrez, Fernando |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6305200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-63052002018-12-26 Genetic analysis reveals functions of atypical polyubiquitin chains Meza Gutierrez, Fernando Simsek, Deniz Mizrak, Arda Deutschbauer, Adam Braberg, Hannes Johnson, Jeffrey Xu, Jiewei Shales, Michael Nguyen, Michelle Tamse-Kuehn, Raquel Palm, Curt Steinmetz, Lars M Krogan, Nevan J Toczyski, David P eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2018-12-14 /pmc/articles/PMC6305200/ /pubmed/30547882 http://dx.doi.org/10.7554/eLife.42955 Text en © 2018, Meza Gutierrez et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Meza Gutierrez, Fernando Simsek, Deniz Mizrak, Arda Deutschbauer, Adam Braberg, Hannes Johnson, Jeffrey Xu, Jiewei Shales, Michael Nguyen, Michelle Tamse-Kuehn, Raquel Palm, Curt Steinmetz, Lars M Krogan, Nevan J Toczyski, David P Genetic analysis reveals functions of atypical polyubiquitin chains |
title | Genetic analysis reveals functions of atypical polyubiquitin chains |
title_full | Genetic analysis reveals functions of atypical polyubiquitin chains |
title_fullStr | Genetic analysis reveals functions of atypical polyubiquitin chains |
title_full_unstemmed | Genetic analysis reveals functions of atypical polyubiquitin chains |
title_short | Genetic analysis reveals functions of atypical polyubiquitin chains |
title_sort | genetic analysis reveals functions of atypical polyubiquitin chains |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305200/ https://www.ncbi.nlm.nih.gov/pubmed/30547882 http://dx.doi.org/10.7554/eLife.42955 |
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