The EMBO Journal
 
Advanced search
Journal home
Aims and scope
Current issue
Advance Online Publication
Web Focuses
Archive:-
Browse by issue
Browse by subject
Browse by category
Free online sample issue
Press releases
Authors & Referees
Editorial process
Guide for authors
Submit an article
Guide for referees
Editorial Team, Senior Advisors and Advisory Editorial Board
Contact Editorial office
Customer services
Subscribe
Order sample copy
Purchase articles
Reprints and permissions
Contact NPG
Advertising
EMBO
www.embo.org
Article
Subject Categories: Signal Transduction | Neuroscience
The EMBO Journal (2006) 25, 1219–1230, doi:10.1038/sj.emboj.7601017
Published online 23 February 2006
Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle
Marçal Vilar1, 3, 4, Maribel Murillo-Carretero1, 3, Helena Mira2, 5, Kalle Magnusson1, Valerie Besset1, 6 and Carlos F Ibáñez1
1 Division of Molecular Neurobiology, Department of Neuroscience, Stockholm, Sweden
2 Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

To whom correspondence should be addressed
Carlos F Ibáñez, Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, Berzelius väg 35, Box 285, Stockholm 17177, Sweden. Tel.: +46 8 524 87660; Fax: +46 8 33 9548; E-mail: carlos.ibanez@neuro.ki.se

3 These authors contributed equally to this work
4 Present address: Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
5 Present address: Departamento de Biologia Celular, Universitat de Valencia, Spain
6 Present address: Sanofi-Aventis, 94400 Vitry sur Seine, France

Received 8 June 2005; Accepted 31 January 2006; Published online 23 February 2006.
Abstract
A screening for intracellular interactors of the p75 neurotrophin receptor (p75NTR) identified brain-expressed X-linked 1 (Bex1), a small adaptor-like protein of unknown function. Bex1 levels oscillated during the cell cycle, and preventing the normal cycling and downregulation of Bex1 in PC12 cells sustained cell proliferation under conditions of growth arrest, and inhibited neuronal differentiation in response to nerve growth factor (NGF). Neuronal differentiation of precursors isolated from the brain subventricular zone was also reduced by ectopic Bex1. In PC12 cells, Bex1 overexpression inhibited the induction of NF-kappaB activity by NGF without affecting activation of Erk1/2 and AKT, while Bex1 knockdown accelerated neuronal differentiation and potentiated NF-kappaB activity in response to NGF. Bex1 competed with RIP2 for binding to the p75NTR intracellular domain, and elevating RIP2 levels restored the ability of cells overexpressing Bex1 to differentiate in response to NGF. Together, these data establish Bex1 as a novel link between neurotrophin signaling, the cell cycle, and neuronal differentiation, and suggest that Bex1 may function by coordinating internal cellular states with the ability of cells to respond to external signals.
Keywords: cell differentiation, growth arrest, NGF, TrkA, PC12 cells
Top

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated

NEWS AND VIEWS

PARsing the events of myelination

Nature Neuroscience News and Views (01 Jan 2007)

Axon growth inhibition: signals from the p75 neurotrophin receptor

Nature Neuroscience News and Views (01 May 2003)

See all 3 matches for News And Views

Send to a friendEmail link to a friend
PDFDownload PDF
Full textFull text
Next article
Previous article
Table of contents
rights and permissionsRights and permissions
order commercial reprintsReprints
ToC alertRegister for table of contents by email
  Privacy policy Copyright © 2006 by the European Molecular Biology Organization