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The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling
Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth–promoting action in different neuronal systems. Whereas FAIM overe...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172486/ https://www.ncbi.nlm.nih.gov/pubmed/15520226 http://dx.doi.org/10.1083/jcb.200403093 |
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author | Sole, Carme Dolcet, Xavier Segura, Miguel F. Gutierrez, Humberto Diaz-Meco, Maria-Teresa Gozzelino, Raffaella Sanchis, Daniel Bayascas, Jose R. Gallego, Carme Moscat, Jorge Davies, Alun M. Comella, Joan X. |
author_facet | Sole, Carme Dolcet, Xavier Segura, Miguel F. Gutierrez, Humberto Diaz-Meco, Maria-Teresa Gozzelino, Raffaella Sanchis, Daniel Bayascas, Jose R. Gallego, Carme Moscat, Jorge Davies, Alun M. Comella, Joan X. |
author_sort | Sole, Carme |
collection | PubMed |
description | Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth–promoting action in different neuronal systems. Whereas FAIM overexpression greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-κB activation, and blocking this activation by using a super-repressor IκBα or by carrying out experiments using cortical neurons from mice that lack the p65 NF-κB subunit prevented FAIM-induced neurite outgrowth. The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras–ERK pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin receptor NGF receptors in a ligand-dependent manner. These results reveal a new function of FAIM in promoting neurite outgrowth by a mechanism involving activation of the Ras–ERK pathway and NF-κB. |
format | Text |
id | pubmed-2172486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21724862008-03-05 The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling Sole, Carme Dolcet, Xavier Segura, Miguel F. Gutierrez, Humberto Diaz-Meco, Maria-Teresa Gozzelino, Raffaella Sanchis, Daniel Bayascas, Jose R. Gallego, Carme Moscat, Jorge Davies, Alun M. Comella, Joan X. J Cell Biol Research Articles Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth–promoting action in different neuronal systems. Whereas FAIM overexpression greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-κB activation, and blocking this activation by using a super-repressor IκBα or by carrying out experiments using cortical neurons from mice that lack the p65 NF-κB subunit prevented FAIM-induced neurite outgrowth. The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras–ERK pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin receptor NGF receptors in a ligand-dependent manner. These results reveal a new function of FAIM in promoting neurite outgrowth by a mechanism involving activation of the Ras–ERK pathway and NF-κB. The Rockefeller University Press 2004-11-08 /pmc/articles/PMC2172486/ /pubmed/15520226 http://dx.doi.org/10.1083/jcb.200403093 Text en Copyright © 2004, The Rockefeller University Press https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/ (https://creativecommons.org/licenses/by-nc-sa/4.0/) ). |
spellingShingle | Research Articles Sole, Carme Dolcet, Xavier Segura, Miguel F. Gutierrez, Humberto Diaz-Meco, Maria-Teresa Gozzelino, Raffaella Sanchis, Daniel Bayascas, Jose R. Gallego, Carme Moscat, Jorge Davies, Alun M. Comella, Joan X. The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title | The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title_full | The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title_fullStr | The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title_full_unstemmed | The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title_short | The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling |
title_sort | death receptor antagonist faim promotes neurite outgrowth by a mechanism that depends on erk and nf-κb signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172486/ https://www.ncbi.nlm.nih.gov/pubmed/15520226 http://dx.doi.org/10.1083/jcb.200403093 |
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