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Changes in the Concentration of Markers Participating in the Regulation of the Apoptosis Receptor Pathway Involving Soluble Tumour Necrosis Factor Ligand Inducing Apoptosis (sTRAIL) and Osteoprotegerin (OPG) in the Serum of Women with Ovarian Cancer—Participation in Pathogenesis or a Possible Clinical Use?
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On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function

Immunobiology Laboratories, Massachusetts General Hospital, 13th Street, Building 149, Rm. 3602, Boston, MA 02129, USA
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Cells 2020, 9(3), 764; https://doi.org/10.3390/cells9030764
Received: 2 February 2020 / Revised: 16 March 2020 / Accepted: 17 March 2020 / Published: 20 March 2020
(This article belongs to the Special Issue TRAIL Receptors in Health and Diseases)
Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with a focus on structure-function. Using combinatorics, we argue that receptors that cluster on the cell surface and are activated by membrane-bound ligands need to arrange in a highly ordered manner, as the probability of random ligand and receptor arrangements matching up for receptor activation is very low. A growing body of evidence indicates that antiparallel receptor dimers that sequester the ligand binding site cluster on the cell surface, forming a hexagonal lattice. Upon ligand binding, this arrangement puts the activated receptors at the right distance to accommodate the downstream signaling partners. The data also suggest that the same geometry is utilized regardless of receptor type. The unified model provides important clues about TNF receptor signaling and should aid the design of better therapies for cancer and various immune mediated diseases. View Full-Text
Keywords: TRAIL; TRAIL receptors; apoptosis; TNFSF signaling; receptor clustering; antiparallel dimer; hexagonal lattice; cancer TRAIL; TRAIL receptors; apoptosis; TNFSF signaling; receptor clustering; antiparallel dimer; hexagonal lattice; cancer
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Vanamee, É.S.; Faustman, D.L. On the TRAIL of Better Therapies: Understanding TNFRSF Structure-Function. Cells 2020, 9, 764.

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