Home > Articles > Published articles > X-linked Inhibitor of Apoptosis Protein negatively regulates neuronal differentiation through interaction with cRAF and Trk |
Date: | 2013 |
Abstract: | X-linked Inhibitor of apoptosis protein (XIAP) has been classically identified as a cell death regulator. Here, we demonstrate a novel function of XIAP as a regulator of neurite outgrowth in neuronal cells. In PC12 cells, XIAP overexpression prevents NGF-induced neuronal differentiation, whereas NGF treatment induces a reduction of endogenous XIAP levels concomitant with the induction of neuronal differentiation. Accordingly, downregulation of endogenous XIAP protein levels strongly increases neurite outgrowth in PC12 cells as well as axonal and dendritic length in primary cortical neurons. The effects of XIAP are mediated by the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERKs) pathway since blocking this pathway completely prevents the neuritogenesis mediated by XIAP downregulation. In addition, we found that XIAP binds to cRaf and Trk receptors. Our results demonstrate that XIAP plays a new role as a negative regulator of neurotrophin-induced neurite outgrowth and neuronal differentiation in developing neurons. |
Grants: | Ministerio de Ciencia e Innovación SAF2011-30281 Ministerio de Ciencia e Innovación SAF2010-19953 Ministerio de Ciencia e Innovación SAF2010-20925 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-1231 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-346 |
Note: | Altres ajuts: CIBERNED CB06/05/0042 i CB06/05/1104, RENEVAS RD06/0026/1009 i Juan de la Cierva |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Language: | Anglès |
Document: | Article ; Versió publicada |
Subject: | Neurociència ; Factors neurotròfics ; Neurociència cel·lular ; Creixement cel·lular ; Neuroquímica ; Neurotrophic factors ; Cellular neuroscience ; Cell growth ; Neurochemistry |
Published in: | Scientific reports, Vol. 3 (August 2013) , p. 2397, ISSN 2045-2322 |
11 p, 1.7 MB |
Supplementary information 4 p, 2.1 MB |