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Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo
Arginyltransferase1 (ATE1) is a conserved enzyme in eukaryotes mediating posttranslational arginylation, the addition of an extra arginine to an existing protein. In mammals, the dysregulations of the ATE1 gene (ate1) is shown to be involved in cardiovascular abnormalities, cancer, and aging-related...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218141/ https://www.ncbi.nlm.nih.gov/pubmed/32435206 http://dx.doi.org/10.3389/fphys.2020.00427 |
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author | Wiley, David J. D’Urso, Gennaro Zhang, Fangliang |
author_facet | Wiley, David J. D’Urso, Gennaro Zhang, Fangliang |
author_sort | Wiley, David J. |
collection | PubMed |
description | Arginyltransferase1 (ATE1) is a conserved enzyme in eukaryotes mediating posttranslational arginylation, the addition of an extra arginine to an existing protein. In mammals, the dysregulations of the ATE1 gene (ate1) is shown to be involved in cardiovascular abnormalities, cancer, and aging-related diseases. Although biochemical evidence suggested that arginylation may be involved in stress response and/or protein degradation, the physiological role of ATE1 in vivo has never been systematically determined. This gap of knowledge leads to difficulties for interpreting the involvements of ATE1 in diseases pathogenesis. Since ate1 is highly conserved between human and the unicellular organism Schizosaccharomyces pombe (S. pombe), we take advantage of the gene-knockout library of S. pombe, to investigate the genetic interactions between ate1 and other genes in a systematic and unbiased manner. By this approach, we found that ate1 has a surprisingly small and focused impact size. Among the 3659 tested genes, which covers nearly 75% of the genome of S. pombe, less than 5% of them displayed significant genetic interactions with ate1. Furthermore, these ate1-interacting partners can be grouped into a few discrete clustered categories based on their functions or their physical interactions. These categories include translation/transcription regulation, biosynthesis/metabolism of biomolecules (including histidine), cell morphology and cellular dynamics, response to oxidative or metabolic stress, ribosomal structure and function, and mitochondrial function. Unexpectedly, inconsistent to popular belief, very few genes in the global ubiquitination or degradation pathways showed interactions with ate1. Our results suggested that ATE1 specifically regulates a handful of cellular processes in vivo, which will provide critical mechanistic leads for studying the involvements of ATE1 in normal physiologies as well as in diseased conditions. |
format | Online Article Text |
id | pubmed-7218141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72181412020-05-20 Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo Wiley, David J. D’Urso, Gennaro Zhang, Fangliang Front Physiol Physiology Arginyltransferase1 (ATE1) is a conserved enzyme in eukaryotes mediating posttranslational arginylation, the addition of an extra arginine to an existing protein. In mammals, the dysregulations of the ATE1 gene (ate1) is shown to be involved in cardiovascular abnormalities, cancer, and aging-related diseases. Although biochemical evidence suggested that arginylation may be involved in stress response and/or protein degradation, the physiological role of ATE1 in vivo has never been systematically determined. This gap of knowledge leads to difficulties for interpreting the involvements of ATE1 in diseases pathogenesis. Since ate1 is highly conserved between human and the unicellular organism Schizosaccharomyces pombe (S. pombe), we take advantage of the gene-knockout library of S. pombe, to investigate the genetic interactions between ate1 and other genes in a systematic and unbiased manner. By this approach, we found that ate1 has a surprisingly small and focused impact size. Among the 3659 tested genes, which covers nearly 75% of the genome of S. pombe, less than 5% of them displayed significant genetic interactions with ate1. Furthermore, these ate1-interacting partners can be grouped into a few discrete clustered categories based on their functions or their physical interactions. These categories include translation/transcription regulation, biosynthesis/metabolism of biomolecules (including histidine), cell morphology and cellular dynamics, response to oxidative or metabolic stress, ribosomal structure and function, and mitochondrial function. Unexpectedly, inconsistent to popular belief, very few genes in the global ubiquitination or degradation pathways showed interactions with ate1. Our results suggested that ATE1 specifically regulates a handful of cellular processes in vivo, which will provide critical mechanistic leads for studying the involvements of ATE1 in normal physiologies as well as in diseased conditions. Frontiers Media S.A. 2020-05-06 /pmc/articles/PMC7218141/ /pubmed/32435206 http://dx.doi.org/10.3389/fphys.2020.00427 Text en Copyright © 2020 Wiley, D’Urso and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Wiley, David J. D’Urso, Gennaro Zhang, Fangliang Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title | Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title_full | Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title_fullStr | Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title_full_unstemmed | Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title_short | Posttranslational Arginylation Enzyme Arginyltransferase1 Shows Genetic Interactions With Specific Cellular Pathways in vivo |
title_sort | posttranslational arginylation enzyme arginyltransferase1 shows genetic interactions with specific cellular pathways in vivo |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218141/ https://www.ncbi.nlm.nih.gov/pubmed/32435206 http://dx.doi.org/10.3389/fphys.2020.00427 |
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