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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...

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Detalles Bibliográficos
Autores principales: Rossi, Nicholas A., Mora, Thierry, Walczak, Aleksandra M., Dunlop, Mary J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
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.
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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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