About this Research Topic
The TNF superfamily is composed of 19 ligands and 30 receptors, with all members representing therapeutically relevant targets in a plethora of human diseases. TNF family ligands are type II membrane-bound proteins sharing a common structural motif that mediates ligand trimerization: the TNF homology domain. Each subunit of the trimer binds to one TNF receptor (TNFR) subunit, inducing the oligomerization of the receptor that generates the minimal active unit in most members of the family. Nevertheless, the ability to transduce a specific signal following ligand binding depends on the integration of several factors, such as ligand architecture, assembly of receptor units in a ligand-independent manner, posttranslational modifications, transmembrane helix associations and, most probably, additional events that still remain elusive.
Although the impact of ligand oligomerization in signal transduction has been extensively studied, our knowledge of the mechanistic driving signal transduction by synthetic ligands, peptide mimetics, agonistic or antagonistic antibodies remain scarce. It has become clear that receptor clustering on the cell membrane cannot solely be attributed to ligand binding. Instead, ligand-independent associations, posttranslational modifications and transmembrane helix associations, among others, can shape the ability of a receptor to transduce a specific signal following ligand binding or even independently of the ligand. For this reason, it is essential to gain new insights into receptor oligomerization and signaling.
The aim of the current Research Topic is to assemble novel and promising trends in the TNF superfamily field that allow us to expand our knowledge of the control of signal transduction and the diversity of signals that can be triggered under specific conditions. Topics covered may include, but are not limited to:
• Relationship between receptor oligomerization and signaling.
• Ligand architecture and signaling.
• Membrane organization of receptor complexes.
• Differential recruitment of signal adaptor molecules.
• Alternative signal transduction pathways.
• Posttranslational modifications affecting TNFR signal transduction.
• Therapeutic strategies to control signaling outcomes.
Contributions to this Research Topic may include, but are not limited to, the following article types: original research, review, case report, empirical study, mini review, data report, opinion.
Keywords: TNFR, Oligomerization, Ligand Architecture, Signal Adaptor Molecules, Posttranslational Modifications
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