RGD Reference Report - Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle. - Rat Genome Database

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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.
RGD ID: 8554704
Pubmed: PMID:16498402   (View Abstract at PubMed)
PMCID: PMC1422154   (View Article at PubMed Central)
DOI: DOI:10.1038/sj.emboj.7601017   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron differentiation acts_upstream_of_or_withinIDA 8554704PMID:16498402MGI 
positive regulation of neuroblast proliferation acts_upstream_of_or_withinIDA 8554704PMID:16498402MGI 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 8554704PMID:16498402MGI 
nucleus located_inIDA 8554704PMID:16498402MGI 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P071748554704PMID:16498402IntAct 
protein binding enablesIPIUniProtKB:Q3MKQ28554704PMID:16498402IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Bex1  (brain expressed X-linked 1)
Ngfr  (nerve growth factor receptor)

Objects referenced in this article
Gene Bex2 brain expressed X-linked 2 Rattus norvegicus

Additional Information