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Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target
To understand disease mechanisms, a large-scale analysis of human–yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human–yeast genetic interactions were identified by en masse transformation of the human disease genes into a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580709/ https://www.ncbi.nlm.nih.gov/pubmed/28596290 http://dx.doi.org/10.1101/gr.211649.116 |
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author | Jo, Myungjin Chung, Ah Young Yachie, Nozomu Seo, Minchul Jeon, Hyejin Nam, Youngpyo Seo, Yeojin Kim, Eunmi Zhong, Quan Vidal, Marc Park, Hae Chul Roth, Frederick P. Suk, Kyoungho |
author_facet | Jo, Myungjin Chung, Ah Young Yachie, Nozomu Seo, Minchul Jeon, Hyejin Nam, Youngpyo Seo, Yeojin Kim, Eunmi Zhong, Quan Vidal, Marc Park, Hae Chul Roth, Frederick P. Suk, Kyoungho |
author_sort | Jo, Myungjin |
collection | PubMed |
description | To understand disease mechanisms, a large-scale analysis of human–yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human–yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport. When yeast genetic interaction partners held in common between human OPTN and ANG were validated in mammalian cells and zebrafish, MAP2K5 kinase emerged as a potential drug target for ALS therapy. The toxicity modifiers identified in this study may deepen our understanding of the pathogenic mechanisms of ALS and other devastating diseases. |
format | Online Article Text |
id | pubmed-5580709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-55807092017-09-14 Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target Jo, Myungjin Chung, Ah Young Yachie, Nozomu Seo, Minchul Jeon, Hyejin Nam, Youngpyo Seo, Yeojin Kim, Eunmi Zhong, Quan Vidal, Marc Park, Hae Chul Roth, Frederick P. Suk, Kyoungho Genome Res Research To understand disease mechanisms, a large-scale analysis of human–yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human–yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin (OPTN) and angiogenin (ANG), showed that the human orthologs of the yeast toxicity modifiers of these ALS genes are enriched for several biological processes, such as cell death, lipid metabolism, and molecular transport. When yeast genetic interaction partners held in common between human OPTN and ANG were validated in mammalian cells and zebrafish, MAP2K5 kinase emerged as a potential drug target for ALS therapy. The toxicity modifiers identified in this study may deepen our understanding of the pathogenic mechanisms of ALS and other devastating diseases. Cold Spring Harbor Laboratory Press 2017-09 /pmc/articles/PMC5580709/ /pubmed/28596290 http://dx.doi.org/10.1101/gr.211649.116 Text en © 2017 Jo et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Jo, Myungjin Chung, Ah Young Yachie, Nozomu Seo, Minchul Jeon, Hyejin Nam, Youngpyo Seo, Yeojin Kim, Eunmi Zhong, Quan Vidal, Marc Park, Hae Chul Roth, Frederick P. Suk, Kyoungho Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title | Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title_full | Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title_fullStr | Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title_full_unstemmed | Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title_short | Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target |
title_sort | yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of map2k5 kinase as a potential drug target |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580709/ https://www.ncbi.nlm.nih.gov/pubmed/28596290 http://dx.doi.org/10.1101/gr.211649.116 |
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