Exploring a Novel Mechanism of Reguation of the TNFR Family Member FN14
type: CreativeWork
description: Fibroblast growth factor-inducible 14 (FN14) is a highly inducible cytokine receptor linked to a number of intracellular signaling pathways, including the nuclear factor-kappaB (NFkB) and mitogen-activated protein kinase (MAPK) pathways, as well as to physiological processes, such as angiogenesis, tissue repair, and regeneration. Although FN14 is expressed at low levels in normal tissue, it is highly expressed after tissue injury and appears to mediate activities crucial to wound repair and regeneration. In vitro, FN14 expression is induced by numerous growth factors, as well as by its own ligand TNF-like weak inducer of apoptosis (TWEAK). Given these results, it is thought that FN14 plays an important physiological role in the response to acute injury, and that FN14 activity is primarily regulated at the level of ligand and receptor expression. Various pathological states, however, also exhibit increased expression and activity of FN14. Tumor progression, chronic autoimmune disease, and neuroinflammation are just a few of the conditions in which increased expression or function of FN14 have been implicated. In addition, it has been shown, in vitro, that overexpression of FN14 can result in ligand-independent signaling by the receptor. This signaling in the absence of TWEAK has been associated with increased proliferation and invasiveness of several types of cancer cells. Thus, although FN14 plays an important physiological role after acute injury, it appears that dysregulation of FN14 expression may contribute to various chronic pathological states. Since FN14 protein expression is so highly inducible, and TWEAK-FN14 signaling can further amplify receptor levels, this begs the question whether unregulated receptor levels can influence the pathological switch through altered signaling and resultant cell proliferation, migration, or chemokine expression. It seems likely that there are cellular mechanisms in place to prevent excess accumulation of FN14. To date, howev…
abstract: Fibroblast growth factor-inducible 14 (FN14) is a highly inducible cytokine receptor linked to a number of intracellular signaling pathways, including the nuclear factor-kappaB (NFkB) and mitogen-activated protein kinase (MAPK) pathways, as well as to physiological processes, such as angiogenesis, tissue repair, and regeneration. Although FN14 is expressed at low levels in normal tissue, it is highly expressed after tissue injury and appears to mediate activities crucial to wound repair and regeneration. In vitro, FN14 expression is induced by numerous growth factors, as well as by its own ligand TNF-like weak inducer of apoptosis (TWEAK). Given these results, it is thought that FN14 plays an important physiological role in the response to acute injury, and that FN14 activity is primarily regulated at the level of ligand and receptor expression. Various pathological states, however, also exhibit increased expression and activity of FN14. Tumor progression, chronic autoimmune disease, and neuroinflammation are just a few of the conditions in which increased expression or function of FN14 have been implicated. In addition, it has been shown, in vitro, that overexpression of FN14 can result in ligand-independent signaling by the receptor. This signaling in the absence of TWEAK has been associated with increased proliferation and invasiveness of several types of cancer cells. Thus, although FN14 plays an important physiological role after acute injury, it appears that dysregulation of FN14 expression may contribute to various chronic pathological states. Since FN14 protein expression is so highly inducible, and TWEAK-FN14 signaling can further amplify receptor levels, this begs the question whether unregulated receptor levels can influence the pathological switch through altered signaling and resultant cell proliferation, migration, or chemokine expression. It seems likely that there are cellular mechanisms in place to prevent excess accumulation of FN14. To date, howev…
author: Gurunathan, Sujatha
language: English
keywords: Immunology
date published: 2012
date modified: 2026-07-24T01:44:18Z
provider: Columbia University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Columbia University

PropertyValue
property ID: DOI
value: 10.7916/D8J96DGM