RGD Reference Report - TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction. - Rat Genome Database

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TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction.

Authors: Ye, X  Mehlen, P  Rabizadeh, S  VanArsdale, T  Zhang, H  Shin, H  Wang, JJ  Leo, E  Zapata, J  Hauser, CA  Reed, JC  Bredesen, DE 
Citation: Ye X, etal., J Biol Chem. 1999 Oct 15;274(42):30202-8.
RGD ID: 8554701
Pubmed: PMID:10514511   (View Abstract at PubMed)

The common neurotrophin receptor, p75(NTR), has been shown to signal in the absence of Trk tyrosine kinase receptors, including induction of neural apoptosis and activation of NF-kappaB. However, the mechanisms by which p75(NTR) initiates these intracellular signal transduction pathways are unknown. Here we report interactions between p75(NTR) and the six members of TRAF (tumor necrosis factor receptor-associated factors) family proteins. The binding of different TRAF proteins to p75(NTR) was mapped to distinct regions in p75(NTR). Furthermore, TRAF4 interacted with dimeric p75(NTR), whereas TRAF2 interacted preferentially with monomeric p75(NTR). TRAF2-p75(NTR), TRAF4-p75(NTR), and TRAF6-p75(NTR) interactions modulated p75(NTR)-induced cell death and NF-kappaB activation with contrasting effects. Coexpression of TRAF2 with p75(NTR) enhanced cell death, whereas coexpression of TRAF6 was cytoprotective. Furthermore, overexpression of TRAF4 abrogated the ability of dimerization to prevent the induction of apoptosis normally mediated by monomeric p75(NTR). TRAF4 also inhibited the NF-kappaB response, whereas TRAF2 and TRAF6 enhanced p75(NTR)-induced NF-kappaB activation. These results demonstrate that TRAF family proteins interact with p75(NTR) and differentially modulate its NF-kappaB activation and cell death induction.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q129338554701PMID:10514511IntAct 
protein binding enablesIPIUniProtKB:Q9BUZ48554701PMID:10514511IntAct 
protein binding enablesIPIUniProtKB:Q9Y4K38554701PMID:10514511IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Ngfr  (nerve growth factor receptor)


Additional Information