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Active degradation of MarA controls coordination of its downstream targets
Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how the multiple antibiotic resistance activator MarA coordinates its downstream targets. MarA controls a variety of stress response ge...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307708/ https://www.ncbi.nlm.nih.gov/pubmed/30589845 http://dx.doi.org/10.1371/journal.pcbi.1006634 |
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author | Rossi, Nicholas A. Mora, Thierry Walczak, Aleksandra M. Dunlop, Mary J. |
author_facet | Rossi, Nicholas A. Mora, Thierry Walczak, Aleksandra M. Dunlop, Mary J. |
author_sort | Rossi, Nicholas A. |
collection | PubMed |
description | Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how the multiple antibiotic resistance activator MarA coordinates its downstream targets. MarA controls a variety of stress response genes in Escherichia coli. We modify its half-life either by knocking down the protease that targets it via CRISPRi or by engineering MarA to protect it from degradation. Our experimental and analytical results indicate that active degradation can impact both the rate of coordination and the maximum coordination that downstream genes can achieve. In the context of multi-gene regulation, trade-offs between these properties show that perfect information fidelity and instantaneous coordination cannot coexist. |
format | Online Article Text |
id | pubmed-6307708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-63077082019-01-08 Active degradation of MarA controls coordination of its downstream targets Rossi, Nicholas A. Mora, Thierry Walczak, Aleksandra M. Dunlop, Mary J. PLoS Comput Biol Research Article Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how the multiple antibiotic resistance activator MarA coordinates its downstream targets. MarA controls a variety of stress response genes in Escherichia coli. We modify its half-life either by knocking down the protease that targets it via CRISPRi or by engineering MarA to protect it from degradation. Our experimental and analytical results indicate that active degradation can impact both the rate of coordination and the maximum coordination that downstream genes can achieve. In the context of multi-gene regulation, trade-offs between these properties show that perfect information fidelity and instantaneous coordination cannot coexist. Public Library of Science 2018-12-27 /pmc/articles/PMC6307708/ /pubmed/30589845 http://dx.doi.org/10.1371/journal.pcbi.1006634 Text en © 2018 Rossi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Rossi, Nicholas A. Mora, Thierry Walczak, Aleksandra M. Dunlop, Mary J. Active degradation of MarA controls coordination of its downstream targets |
title | Active degradation of MarA controls coordination of its downstream targets |
title_full | Active degradation of MarA controls coordination of its downstream targets |
title_fullStr | Active degradation of MarA controls coordination of its downstream targets |
title_full_unstemmed | Active degradation of MarA controls coordination of its downstream targets |
title_short | Active degradation of MarA controls coordination of its downstream targets |
title_sort | active degradation of mara controls coordination of its downstream targets |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307708/ https://www.ncbi.nlm.nih.gov/pubmed/30589845 http://dx.doi.org/10.1371/journal.pcbi.1006634 |
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