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Yeast-Based Genetic Interaction Analysis of Human Kinome

1
Department 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, Korea
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School of Life Sciences, Brain Korea 21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
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Donnelly Centre and Departments of Molecular Genetics and Computer Science, University of Toronto and Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada
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Department of Biological Sciences, Wright State University, Dayton, OH 45435, USA
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Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
Present address: Korea Brain Research Institute, Daegu, Korea.
Present address: Synthetic Biology Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; Institute for Advanced Bioscience, Keio University, Tsuruoka, Yamagata, Japan; PRESTO, Japan Science and Technology Agency (JST), Tokyo 153-8904, Japan.
Cells 2020, 9(5), 1156; https://doi.org/10.3390/cells9051156
Received: 11 April 2020 / Revised: 24 April 2020 / Accepted: 4 May 2020 / Published: 7 May 2020
(This article belongs to the Section Cell Signaling)
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. En masse 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. View Full-Text
Keywords: yeast; kinase; genetic interaction; network; bar-seq yeast; kinase; genetic interaction; network; bar-seq
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MDPI and ACS Style

Kim, J.-H.; Seo, Y.; Jo, M.; Jeon, H.; Lee, W.-H.; Yachie, N.; Zhong, Q.; Vidal, M.; Roth, F.P.; Suk, K. Yeast-Based Genetic Interaction Analysis of Human Kinome. Cells 2020, 9, 1156. https://doi.org/10.3390/cells9051156

AMA Style

Kim J-H, Seo Y, Jo M, Jeon H, Lee W-H, Yachie N, Zhong Q, Vidal M, Roth FP, Suk K. Yeast-Based Genetic Interaction Analysis of Human Kinome. Cells. 2020; 9(5):1156. https://doi.org/10.3390/cells9051156

Chicago/Turabian Style

Kim, Jae-Hong, Yeojin Seo, Myungjin Jo, Hyejin Jeon, Won-Ha Lee, Nozomu Yachie, Quan Zhong, Marc Vidal, Frederick P. Roth, and Kyoungho Suk. 2020. "Yeast-Based Genetic Interaction Analysis of Human Kinome" Cells 9, no. 5: 1156. https://doi.org/10.3390/cells9051156

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