TY  - INPR
A1  - Amstein, Leonie Katharina
A1  - Ackermann, Jörg
A1  - Hannig, Jennifer
A1  - Đikić, Ivan
A1  - Fulda, Simone
A1  - Koch, Ina
T1  - Mathematical modeling of the molecular switch of TNFR1-mediated signaling pathways using Petri nets
T2  - bioRxiv
N2  - The paper describes a mathematical model of the molecular switch of cell survival, apoptosis, and necroptosis in cellular signaling pathways initiated by tumor necrosis factor 1. Based on experimental findings in the current literature, we constructed a Petri net model in terms of detailed molecular reactions for the molecular players, protein complexes, post-translational modifications, and cross talk. The model comprises 118 biochemical entities, 130 reactions, and 299 connecting edges. Applying Petri net analysis techniques, we found 279 pathways describing complete signal flows from receptor activation to cellular response, representing the combinatorial diversity of functional pathways.120 pathways steered the cell to survival, whereas 58 and 35 pathways led to apoptosis and necroptosis, respectively. For 65 pathways, the triggered response was not deterministic, leading to multiple possible outcomes. Based on the Petri net, we investigated the detailed in silico knockout behavior and identified important checkpoints of the TNFR1 signaling pathway in terms of ubiquitination within complex I and the gene expression dependent on NF-κB, which controls the caspase activity in complex II and apoptosis induction.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72964
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-729642
IS  - 2021.11.02.466901
ER  -