Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
Dr. Mendik, Péter
Department of Molecular Biology
+36304740319
petermendik@gmail.com
Translocating proteins compartment-specifically alter the fate of epithelial-mesenchymal transition in a compartmentalized Boolean network model
Péter Mendik1#, Márk Kerestély1#, Sebestyén Kamp2, Dávid Deritei1, Nina Kunšič1, Zsolt Vassy1, Péter Csermely1, Daniel V. Veres1,2
1Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary
2Turbine Ltd. Budapest, Hungary
#The authors wish it to be known, that the first two authors should be regarded as Joint First Authors.
Szóbeli
Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
English
Molecular Sciences
Epithelial-mesenchymal transition (EMT) plays a pivotal role in cellular processes, such as embryonic development, wound healing or cancer progression. Amongst orchestrators of EMT we can find several translocating proteins, such as key transcription factors (e.g.: β-catenin). The regulation of translocating proteins defines cellular behaviour.
We described how protein translocation generally affects cellular regulation through systematically incorporating protein translocation into an in silico Boolean dynamic signalling model.
Highlighting their role, translocating proteins become enriched in EMT-signalling. We created a compartmentalized Boolean network model in order to simulate the compartment-specific functions of translocating proteins.
Our model 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 and among 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 similar to ours, will be useful to understand subcellular processes and to create more complex drug targeting strategies.
This work was supported by the ÚNKP-20-III-2-SE-23 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation fund, through the EFOP-3.6.3-VEKOP-16-2017-00009 (titled: “Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése) programme, by the Hungarian National Research, Development and Innovation Office [K131458], by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Molecular Biology thematic programmes of Semmelweis University, by the Thematic Excellence Programme (Tématerületi Kiválósági Program, 2020-4.1.1.-TKP2020, TKP-2021-EGA-24) of the Ministry for Innovation and Technology in Hungary, within the framework of the Molecular Biology thematic programme of the Semmelweis University.
Semmelweis University, Doctoral School of Molecular Medicine
Prof Péter Csermely, Dániel Veres MD PhD
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
4782
12:15
12:30
Péter Mendik1#, Márk Kerestély1#, Sebestyén Kamp2, Dávid Deritei1, Nina Kunšič1, Zsolt Vassy1, Péter Csermely1, Daniel V. Veres1,2
1Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary
2Turbine Ltd. Budapest, Hungary
#The authors wish it to be known, that the first two authors should be regarded as Joint First Authors.