Frequency-preference response in covalent modification cycles under substrate sequestration conditions

Abstract Covalent modification cycles (CMCs) are basic units of signaling systems and their properties are well understood. However, their behavior has been mostly characterized in situations where the substrate is in excess over the modifying enzymes. Experimental data on protein abundance suggest...

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Autores principales:	Juliana Reves Szemere, Horacio G. Rotstein, Alejandra C. Ventura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3aebc1e8cc694cfd8280cb1feb64b81b
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spelling	oai:doaj.org-article:3aebc1e8cc694cfd8280cb1feb64b81b2021-12-02T18:51:40ZFrequency-preference response in covalent modification cycles under substrate sequestration conditions10.1038/s41540-021-00192-82056-7189https://doaj.org/article/3aebc1e8cc694cfd8280cb1feb64b81b2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41540-021-00192-8https://doaj.org/toc/2056-7189Abstract Covalent modification cycles (CMCs) are basic units of signaling systems and their properties are well understood. However, their behavior has been mostly characterized in situations where the substrate is in excess over the modifying enzymes. Experimental data on protein abundance suggest that the enzymes and their target proteins are present in comparable concentrations, leading to substrate sequestration by the enzymes. In this enzyme-in-excess regime, CMCs have been shown to exhibit signal termination, the ability of the product to return to a stationary value lower than its peak in response to constant stimulation, while this stimulation is still active, with possible implications for the ability of systems to adapt to environmental inputs. We characterize the conditions leading to signal termination in CMCs in the enzyme-in-excess regime. We also demonstrate that this behavior leads to a preferred frequency response (band-pass filters) when the cycle is subjected to periodic stimulation, whereas the literature reports that CMCs investigated so far behave as low-pass filters. We characterize the relationship between signal termination and the preferred frequency response to periodic inputs and we explore the dynamic mechanism underlying these phenomena. Finally, we describe how the behavior of CMCs is reflected in similar types of responses in the cascades of which they are part. Evidence of protein abundance in vivo shows that enzymes and substrates are present in comparable concentrations, thus suggesting that signal termination and frequency-preference response to periodic inputs are also important dynamic features of cell signaling systems, which have been overlooked.Juliana Reves SzemereHoracio G. RotsteinAlejandra C. VenturaNature PortfolioarticleBiology (General)QH301-705.5ENnpj Systems Biology and Applications, Vol 7, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Juliana Reves Szemere Horacio G. Rotstein Alejandra C. Ventura Frequency-preference response in covalent modification cycles under substrate sequestration conditions
description	Abstract Covalent modification cycles (CMCs) are basic units of signaling systems and their properties are well understood. However, their behavior has been mostly characterized in situations where the substrate is in excess over the modifying enzymes. Experimental data on protein abundance suggest that the enzymes and their target proteins are present in comparable concentrations, leading to substrate sequestration by the enzymes. In this enzyme-in-excess regime, CMCs have been shown to exhibit signal termination, the ability of the product to return to a stationary value lower than its peak in response to constant stimulation, while this stimulation is still active, with possible implications for the ability of systems to adapt to environmental inputs. We characterize the conditions leading to signal termination in CMCs in the enzyme-in-excess regime. We also demonstrate that this behavior leads to a preferred frequency response (band-pass filters) when the cycle is subjected to periodic stimulation, whereas the literature reports that CMCs investigated so far behave as low-pass filters. We characterize the relationship between signal termination and the preferred frequency response to periodic inputs and we explore the dynamic mechanism underlying these phenomena. Finally, we describe how the behavior of CMCs is reflected in similar types of responses in the cascades of which they are part. Evidence of protein abundance in vivo shows that enzymes and substrates are present in comparable concentrations, thus suggesting that signal termination and frequency-preference response to periodic inputs are also important dynamic features of cell signaling systems, which have been overlooked.
format	article
author	Juliana Reves Szemere Horacio G. Rotstein Alejandra C. Ventura
author_facet	Juliana Reves Szemere Horacio G. Rotstein Alejandra C. Ventura
author_sort	Juliana Reves Szemere
title	Frequency-preference response in covalent modification cycles under substrate sequestration conditions
title_short	Frequency-preference response in covalent modification cycles under substrate sequestration conditions
title_full	Frequency-preference response in covalent modification cycles under substrate sequestration conditions
title_fullStr	Frequency-preference response in covalent modification cycles under substrate sequestration conditions
title_full_unstemmed	Frequency-preference response in covalent modification cycles under substrate sequestration conditions
title_sort	frequency-preference response in covalent modification cycles under substrate sequestration conditions
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3aebc1e8cc694cfd8280cb1feb64b81b
work_keys_str_mv	AT julianarevesszemere frequencypreferenceresponseincovalentmodificationcyclesundersubstratesequestrationconditions AT horaciogrotstein frequencypreferenceresponseincovalentmodificationcyclesundersubstratesequestrationconditions AT alejandracventura frequencypreferenceresponseincovalentmodificationcyclesundersubstratesequestrationconditions
_version_	1718377378516828160

Frequency-preference response in covalent modification cycles under substrate sequestration conditions

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