Yeast-Based Genetic Interaction Analysis of Human Kinome
Kinases are critical intracellular signaling proteins. To better understand kinase-mediated signal transduction, a large-scale human–yeast genetic interaction screen was performed. Among 597 human kinase genes tested, 28 displayed strong toxicity in yeast when overexpressed. <i>En masse</i&...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1156 |
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| author | Jae-Hong Kim Yeojin Seo Myungjin Jo Hyejin Jeon Won-Ha Lee Nozomu Yachie Quan Zhong Marc Vidal Frederick P. Roth Kyoungho Suk |
| author_facet | Jae-Hong Kim Yeojin Seo Myungjin Jo Hyejin Jeon Won-Ha Lee Nozomu Yachie Quan Zhong Marc Vidal Frederick P. Roth Kyoungho Suk |
| author_sort | Jae-Hong Kim |
| collection | DOAJ |
| description | Kinases are critical intracellular signaling proteins. To better understand kinase-mediated signal transduction, a large-scale human–yeast genetic interaction screen was performed. Among 597 human kinase genes tested, 28 displayed strong toxicity in yeast when overexpressed. <i>En masse</i> transformation of these toxic kinase genes into 4653 homozygous diploid yeast deletion mutants followed by barcode sequencing identified yeast toxicity modifiers and thus their human orthologs. Subsequent network analyses and functional grouping revealed that the 28 kinases and their 676 interaction partners (corresponding to a total of 969 genetic interactions) are enriched in cell death and survival (34%), small-molecule biochemistry (18%) and molecular transport (11%), among others. In the subnetwork analyses, a few kinases were commonly associated with glioma, cell migration and cell death/survival. Our analysis enabled the creation of a first draft of the kinase genetic interactome network and identified multiple drug targets for inflammatory diseases and cancer, in which deregulated kinase signaling plays a pathogenic role. |
| first_indexed | 2024-03-10T19:58:57Z |
| format | Article |
| id | doaj.art-f809bdb019f2413799fc4946e3bea2f7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:58:57Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f809bdb019f2413799fc4946e3bea2f72023-11-19T23:44:53ZengMDPI AGCells2073-44092020-05-0195115610.3390/cells9051156Yeast-Based Genetic Interaction Analysis of Human KinomeJae-Hong Kim0Yeojin Seo1Myungjin Jo2Hyejin Jeon3Won-Ha Lee4Nozomu Yachie5Quan Zhong6Marc Vidal7Frederick P. Roth8Kyoungho Suk9Department of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, KoreaDepartment of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, KoreaDepartment of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, KoreaDepartment of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, KoreaSchool of Life Sciences, Brain Korea 21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, KoreaDonnelly Centre and Departments of Molecular Genetics and Computer Science, University of Toronto and Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, CanadaDepartment of Biological Sciences, Wright State University, Dayton, OH 45435, USACenter for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USADonnelly Centre and Departments of Molecular Genetics and Computer Science, University of Toronto and Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, CanadaDepartment of Pharmacology, Brain Science and Engineering Institute, and Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, KoreaKinases are critical intracellular signaling proteins. To better understand kinase-mediated signal transduction, a large-scale human–yeast genetic interaction screen was performed. Among 597 human kinase genes tested, 28 displayed strong toxicity in yeast when overexpressed. <i>En masse</i> transformation of these toxic kinase genes into 4653 homozygous diploid yeast deletion mutants followed by barcode sequencing identified yeast toxicity modifiers and thus their human orthologs. Subsequent network analyses and functional grouping revealed that the 28 kinases and their 676 interaction partners (corresponding to a total of 969 genetic interactions) are enriched in cell death and survival (34%), small-molecule biochemistry (18%) and molecular transport (11%), among others. In the subnetwork analyses, a few kinases were commonly associated with glioma, cell migration and cell death/survival. Our analysis enabled the creation of a first draft of the kinase genetic interactome network and identified multiple drug targets for inflammatory diseases and cancer, in which deregulated kinase signaling plays a pathogenic role.https://www.mdpi.com/2073-4409/9/5/1156yeastkinasegenetic interactionnetworkbar-seq |
| spellingShingle | Jae-Hong Kim Yeojin Seo Myungjin Jo Hyejin Jeon Won-Ha Lee Nozomu Yachie Quan Zhong Marc Vidal Frederick P. Roth Kyoungho Suk Yeast-Based Genetic Interaction Analysis of Human Kinome Cells yeast kinase genetic interaction network bar-seq |
| title | Yeast-Based Genetic Interaction Analysis of Human Kinome |
| title_full | Yeast-Based Genetic Interaction Analysis of Human Kinome |
| title_fullStr | Yeast-Based Genetic Interaction Analysis of Human Kinome |
| title_full_unstemmed | Yeast-Based Genetic Interaction Analysis of Human Kinome |
| title_short | Yeast-Based Genetic Interaction Analysis of Human Kinome |
| title_sort | yeast based genetic interaction analysis of human kinome |
| topic | yeast kinase genetic interaction network bar-seq |
| url | https://www.mdpi.com/2073-4409/9/5/1156 |
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