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

Autor: Mendik P; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Kerestély M; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Kamp S; Turbine Ltd, Budapest, Hungary., Deritei D; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Kunšič N; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Vassy Z; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Csermely P; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary., Veres DV; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary. veres.daniel1@med.semmelweis-univ.hu.; Turbine Ltd, Budapest, Hungary. veres.daniel1@med.semmelweis-univ.hu.
Jazyk: angličtina
Zdroj: NPJ systems biology and applications [NPJ Syst Biol Appl] 2022 Jun 09; Vol. 8 (1), pp. 19. Date of Electronic Publication: 2022 Jun 09.
DOI: 10.1038/s41540-022-00228-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje