These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.
Pubmed for Handhelds
PUBMED FOR HANDHELDS
Search MEDLINE/PubMed
Title: Regulation of fibroblast growth factor-inducible 14 (Fn14) expression levels via ligand-independent lysosomal degradation. Author: Gurunathan S, Winkles JA, Ghosh S, Hayden MS. Journal: J Biol Chem; 2014 May 09; 289(19):12976-88. PubMed ID: 24652288. Abstract: Fibroblast growth factor-inducible 14 (Fn14) is a highly inducible cytokine receptor that engages multiple intracellular signaling pathways, including nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). Fn14 expression is regulated by several cytokines and growth factors, and Fn14 is transiently up-regulated after injury. In contrast, in states of chronic inflammatory disease and in some solid tumors, Fn14 is persistently up-regulated. However, the post-translational regulation of Fn14 expression has not been directly investigated. Thus, we examined Fn14 proteostasis in the presence and absence of the Fn14 ligand TNF-like weak inducer of apoptosis (TWEAK). Similar to other TNF receptor superfamily members, we found that TWEAK induces Fn14 internalization and degradation. Surprisingly, we also observed rapid, TWEAK-independent, constitutive Fn14 internalization and turnover. Fn14 levels are maintained in cell culture by ongoing synthesis and trafficking of the receptor, leading to subsequent down-regulation by lysosomal degradation. Unexpectedly, the extracellular domain of Fn14 is necessary and sufficient for constitutive turnover. Based on these findings, we propose a model in which constitutive down-regulation of Fn14 facilitates dynamic regulation of Fn14 protein levels and prevents spontaneous or inappropriate receptor signaling.[Abstract] [Full Text] [Related] [New Search]