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Journal article
Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2
Scientific reports, v 7(1), 6607
26 Jul 2017
PMID: 28747780
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 tm TNF-mimetic scTNF ligands capable of robustly activating TNFR2 and introduce novel TNFR2 agonists that hold promise as therapeutics to treat a variety of diseases.
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Details
- Title
- Novel strategies to mimic transmembrane tumor necrosis factor-dependent activation of tumor necrosis factor receptor 2
- Creators
- Roman Fischer - Drexel UniversityJessica Marsal - University of StuttgartCristiano Gutta - University of StuttgartStephan A. Eisler - University of StuttgartNathalie Peters - University of StuttgartJohn R. Bethea - Drexel UniversityKlaus Pfizenmaier - University of StuttgartRoland E. Kontermann - University of Stuttgart
- Publication Details
- Scientific reports, v 7(1), 6607
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- Az. 0563-2.8./508/2 / Carl Zeiss Foundation grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000406366400015
- Scopus ID
- 2-s2.0-85026365899
- Other Identifier
- 991019169208304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology