%0 Journal Article %1 Fischer2017 %A Fischer, Roman %A Marsal, Jessica %A Guttà, Cristiano %A Eisler, Stephan A. %A Peters, Nathalie %A Bethea, John R. %A Pfizenmaier, Klaus %A Kontermann, Roland E. %D 2017 %I Nature Publishing Group %J Scientific Reports %K 2017 izi kontermann myown pfizenmaier %N 1 %P 6607 %R 10.1038/s41598-017-06993-4 %T Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2 %U http://www.nature.com/articles/s41598-017-06993-4 %V 7 %X © 2017 The Author(s). Tumor necrosis factor receptor 2 (TNFR2) is known to mediate immune suppression and tissue regeneration. Interestingly, the transmembrane form of tumor necrosis factor (tmTNF) is necessary to robustly activate TNFR2. To characterize the stoichiometry and composition of tmTNF during TNFR2 activation, we constructed differently oligomerized single chain TNF ligands (scTNF) comprised of three TNF homology domain (THD) protomers that mimic tmTNF. Using a variety of cellular and in vivo assays, we can show that higher oligomerization of the scTNF trimers results in more efficient TNF/TNFR2 clustering and subsequent signal transduction. Importantly, the three-dimensional orientation of the scTNF trimers impacts the bioactivity of the oligomerized scTNF ligands. Our data unravel the organization of tmTNF-mimetic scTNF ligands capable of robustly activating TNFR2 and introduce novel TNFR2 agonists that hold promise as therapeutic s to treat a variety of diseases. %@ 4159801706

@article{Fischer2017, abstract = {{\textcopyright} 2017 The Author(s). Tumor necrosis factor receptor 2 (TNFR2) is known to mediate immune suppression and tissue regeneration. Interestingly, the transmembrane form of tumor necrosis factor (tmTNF) is necessary to robustly activate TNFR2. To characterize the stoichiometry and composition of tmTNF during TNFR2 activation, we constructed differently oligomerized single chain TNF ligands (scTNF) comprised of three TNF homology domain (THD) protomers that mimic tmTNF. Using a variety of cellular and in vivo assays, we can show that higher oligomerization of the scTNF trimers results in more efficient TNF/TNFR2 clustering and subsequent signal transduction. Importantly, the three-dimensional orientation of the scTNF trimers impacts the bioactivity of the oligomerized scTNF ligands. Our data unravel the organization of tmTNF-mimetic scTNF ligands capable of robustly activating TNFR2 and introduce novel TNFR2 agonists that hold promise as therapeutic s to treat a variety of diseases.}, added-at = {2018-02-01T14:28:34.000+0100}, author = {Fischer, Roman and Marsal, Jessica and Gutt{\`{a}}, Cristiano and Eisler, Stephan A. and Peters, Nathalie and Bethea, John R. and Pfizenmaier, Klaus and Kontermann, Roland E.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2bd42cee4ad192d449af1e38c186e525a/cristiano}, doi = {10.1038/s41598-017-06993-4}, interhash = {5609141fc72ad55115757bb81b4adc29}, intrahash = {bd42cee4ad192d449af1e38c186e525a}, isbn = {4159801706}, issn = {20452322}, journal = {Scientific Reports}, keywords = {2017 izi kontermann myown pfizenmaier}, month = dec, number = 1, pages = 6607, pmid = {28747780}, publisher = {Nature Publishing Group}, timestamp = {2020-02-21T09:41:47.000+0100}, title = {{Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2}}, url = {http://www.nature.com/articles/s41598-017-06993-4}, volume = 7, year = 2017 }