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Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle.

Authors: Vilar, M  Murillo-Carretero, M  Mira, H  Magnusson, K  Besset, V  Ibanez, CF 
Citation: Vilar M, etal., EMBO J. 2006 Mar 22;25(6):1219-30. Epub 2006 Feb 23.
Pubmed: (View Article at PubMed) PMID:16498402
DOI: Full-text: DOI:10.1038/sj.emboj.7601017

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.


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RGD Object Information
RGD ID: 8554704
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.