Usage Information
Citation Information: J Clin Invest. 2001;108(1):143-151. https://doi.org/10.1172/JCI11498.
Abstract
TNF-α is a pleiotropic cytokine activating several signaling pathways initiated at distinct intracellular domains of the TNF receptors. Although the C-terminal region is believed to be responsible for apoptosis induction, the functions of more membrane-proximal domains, including the domain that couples to neutral sphingomyelinase activation, are not yet fully elucidated. The roles of this region and of the associated adapter protein FAN (factor associated with neutral SMase activation) in the cytotoxic response to TNF have been investigated. We have now shown that stable expression in human fibroblasts of a dominant negative form of FAN abrogates TNF-induced ceramide generation from sphingomyelin hydrolysis and reduces caspase processing, thus markedly inhibiting TNF-triggered apoptosis. However, the cytotoxic responses to daunorubicin and exogenous ceramide remain unaltered, as do the TNF-induced p42/p44 MAPK activation and CD54 expression. Fibroblasts from FAN-knockout mice also proved to be resistant to TNF toxicity. These findings highlight the previously unrecognized role of the adapter protein FAN in signaling cell death induction by TNF.
Authors
Bruno Ségui, Olivier Cuvillier, Sabine Adam-Klages, Virginie Garcia, Sophie Malagarie-Cazenave, Sophie Lévêque, Sylvie Caspar-Bauguil, Jérôme Coudert, Robert Salvayre, Martin Krönke, Thierry Levade
Usage data is cumulative from September 2023 through September 2024.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 316 | 34 |
| 111 | 19 | |
| Figure | 285 | 8 |
| Citation downloads | 40 | 0 |
| Totals | 752 | 61 |
| Total Views | 813 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
Copyright © 2024 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)