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Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses

All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleu...

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Autores principales: Petrenko, Natalia, Chereji, Raˇzvan V., McClean, Megan N., Morozov, Alexandre V., Broach, James R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681706/
https://www.ncbi.nlm.nih.gov/pubmed/23615444
http://dx.doi.org/10.1091/mbc.E12-12-0870
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author Petrenko, Natalia
Chereji, Raˇzvan V.
McClean, Megan N.
Morozov, Alexandre V.
Broach, James R.
author_facet Petrenko, Natalia
Chereji, Raˇzvan V.
McClean, Megan N.
Morozov, Alexandre V.
Broach, James R.
author_sort Petrenko, Natalia
collection PubMed
description All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to “hedge their bets” in responding to an uncertain future, and to balance growth and survival in an unpredictable environment.
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spelling pubmed-36817062013-08-30 Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses Petrenko, Natalia Chereji, Raˇzvan V. McClean, Megan N. Morozov, Alexandre V. Broach, James R. Mol Biol Cell Articles All cells perceive and respond to environmental stresses through elaborate stress-sensing networks. Yeast cells sense stress through diverse signaling pathways that converge on the transcription factors Msn2 and Msn4, which respond by initiating rapid, idiosyncratic cycles into and out of the nucleus. To understand the role of Msn2/4 nuclear localization dynamics, we combined time-lapse studies of Msn2-GFP localization in living cells with computational modeling of stress-sensing signaling networks. We find that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osmolarity response mitogen-activated protein kinase pathway, and protein phosphatase 1, regulate activation of Msn2 in distinct ways in response to different stresses. Moreover, we find that bursts of nuclear localization elicit a more robust transcriptional response than does sustained nuclear localization. Using stochastic modeling, we reproduce in silico the responses of Msn2 to different stresses, and demonstrate that bursts of localization arise from noise in the signaling pathways amplified by the small number of Msn2 molecules in the cell. This noise imparts diverse behaviors to genetically identical cells, allowing cell populations to “hedge their bets” in responding to an uncertain future, and to balance growth and survival in an unpredictable environment. The American Society for Cell Biology 2013-06-15 /pmc/articles/PMC3681706/ /pubmed/23615444 http://dx.doi.org/10.1091/mbc.E12-12-0870 Text en © 2013 Petrenko et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Petrenko, Natalia
Chereji, Raˇzvan V.
McClean, Megan N.
Morozov, Alexandre V.
Broach, James R.
Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title_full Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title_fullStr Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title_full_unstemmed Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title_short Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
title_sort noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681706/
https://www.ncbi.nlm.nih.gov/pubmed/23615444
http://dx.doi.org/10.1091/mbc.E12-12-0870
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