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Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model

Regulation of translocating proteins is crucial in defining cellular behaviour. Epithelial-mesenchymal transition (EMT) is important in cellular processes, such as cancer progression. Several orchestrators of EMT, such as key transcription factors, are known to translocate. We show that translocatin...

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Autores principales: Mendik, Péter, Kerestély, Márk, Kamp, Sebestyén, Deritei, Dávid, Kunšič, Nina, Vassy, Zsolt, Csermely, Péter, Veres, Daniel V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184490/
https://www.ncbi.nlm.nih.gov/pubmed/35680961
http://dx.doi.org/10.1038/s41540-022-00228-7
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author Mendik, Péter
Kerestély, Márk
Kamp, Sebestyén
Deritei, Dávid
Kunšič, Nina
Vassy, Zsolt
Csermely, Péter
Veres, Daniel V.
author_facet Mendik, Péter
Kerestély, Márk
Kamp, Sebestyén
Deritei, Dávid
Kunšič, Nina
Vassy, Zsolt
Csermely, Péter
Veres, Daniel V.
author_sort Mendik, Péter
collection PubMed
description Regulation of translocating proteins is crucial in defining cellular behaviour. Epithelial-mesenchymal transition (EMT) is important in cellular processes, such as cancer progression. Several orchestrators of EMT, such as key transcription factors, are known to translocate. We show that translocating proteins become enriched in EMT-signalling. To simulate the compartment-specific functions of translocating proteins we created a compartmentalized Boolean network model. This model successfully reproduced known biological traits of EMT and as a novel feature it also captured organelle-specific functions of proteins. Our results predicted that glycogen synthase kinase-3 beta (GSK3B) compartment-specifically alters the fate of EMT, amongst others the activation of nuclear GSK3B halts transforming growth factor beta-1 (TGFB) induced EMT. Moreover, our results recapitulated that the nuclear activation of glioma associated oncogene transcription factors (GLI) is needed to achieve a complete EMT. Compartmentalized network models will be useful to uncover novel control mechanisms of biological processes. Our algorithmic procedures can be automatically rerun on the https://translocaboole.linkgroup.hu website, which provides a framework for similar future studies.
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spelling pubmed-91844902022-06-11 Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model Mendik, Péter Kerestély, Márk Kamp, Sebestyén Deritei, Dávid Kunšič, Nina Vassy, Zsolt Csermely, Péter Veres, Daniel V. NPJ Syst Biol Appl Article Regulation of translocating proteins is crucial in defining cellular behaviour. Epithelial-mesenchymal transition (EMT) is important in cellular processes, such as cancer progression. Several orchestrators of EMT, such as key transcription factors, are known to translocate. We show that translocating proteins become enriched in EMT-signalling. To simulate the compartment-specific functions of translocating proteins we created a compartmentalized Boolean network model. This model successfully reproduced known biological traits of EMT and as a novel feature it also captured organelle-specific functions of proteins. Our results predicted that glycogen synthase kinase-3 beta (GSK3B) compartment-specifically alters the fate of EMT, amongst others the activation of nuclear GSK3B halts transforming growth factor beta-1 (TGFB) induced EMT. Moreover, our results recapitulated that the nuclear activation of glioma associated oncogene transcription factors (GLI) is needed to achieve a complete EMT. Compartmentalized network models will be useful to uncover novel control mechanisms of biological processes. Our algorithmic procedures can be automatically rerun on the https://translocaboole.linkgroup.hu website, which provides a framework for similar future studies. Nature Publishing Group UK 2022-06-09 /pmc/articles/PMC9184490/ /pubmed/35680961 http://dx.doi.org/10.1038/s41540-022-00228-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Mendik, Péter
Kerestély, Márk
Kamp, Sebestyén
Deritei, Dávid
Kunšič, Nina
Vassy, Zsolt
Csermely, Péter
Veres, Daniel V.
Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title_full Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title_fullStr Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title_full_unstemmed Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title_short Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
title_sort translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized boolean network model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184490/
https://www.ncbi.nlm.nih.gov/pubmed/35680961
http://dx.doi.org/10.1038/s41540-022-00228-7
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