Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling
Cellular Physiology and Biochemistry
Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor-inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14
... on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.