Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2004, PMID: 14960584

A functional interaction between the p75 neurotrophin receptor interacting factors, TRAF6 and NRIF.

Gentry, Jennifer J; Rutkoski, Nancy J; Burke, Tara L; Carter, Bruce D

Neurotrophin signaling through the p75 receptor regulates apoptosis within the nervous system both during development and in response to injury. Whereas a number of p75 interacting factors have been identified, how these upstream factors function in a coordinated manner to mediate receptor signaling is still unclear. Here, we report a functional interaction between TRAF6 and the neurotrophin receptor interacting factor (NRIF), two proteins known to associate with the intracellular domain of the p75 neurotrophin receptor. The association between NRIF and TRAF6 was direct and occurred with both endogenous and ectopically expressed proteins. A KRAB repressor domain of NRIF and the carboxyl-terminal, receptor-binding region of TRAF6 were required for the interaction. Co-expression of TRAF6 increased the levels of NRIF protein and induced its nuclear translocation. Reciprocally, NRIF enhanced TRAF6-mediated activation of the c-Jun NH2-terminal kinase (JNK) by 3-fold, while only modestly increasing the stimulation of NF-kappaB. The expression of both NRIF and TRAF6 was required for reconstituting p75 activation of JNK in HEK293 cells, whereas NRIF mutants lacking the TRAF6 interaction domain were unable to substitute for the full-length protein in facilitating activation of the kinase. These results suggest that NRIF and TRAF6 functionally interact to facilitate neurotrophin signaling through the p75 receptor.

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Text Mining Data

c-Jun NH2-terminal kinase (JNK) → TRAF6: " Reciprocally, NRIF enhanced TRAF6 mediated activation of the c-Jun NH2-terminal kinase (JNK) by 3-fold, while only modestly increasing the stimulation of NF-kappaB "

c-Jun NH2-terminal kinase (JNK) → NF-kappaB: " Reciprocally, NRIF enhanced TRAF6 mediated activation of the c-Jun NH2-terminal kinase (JNK) by 3-fold, while only modestly increasing the stimulation of NF-kappaB "

Manually curated Databases

  • IRef Biogrid Interaction: TRAF6 — NGFR (direct interaction, pull down)
  • IRef Biogrid Interaction: TRAF6 — NGFR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: NGFR — NGFR (direct interaction, pull down)
  • NCI Pathway Database p75(NTR)-mediated signaling: JNK family-active (MAPK8/MAPK9/MAPK10) → JNK family (MAPK8/MAPK9/MAPK10) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: JNK family (MAPK8/MAPK9/MAPK10) → proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF complex (NGF-NGFR-SORT1-TRAF6-ZNF274) (modification, collaborate)
    Evidence: mutant phenotype, assay, reporter gene, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6 complex (NGFR-BDNF-SORT1-TRAF6) → NRIF (ZNF274) (modification, collaborate)
    Evidence: mutant phenotype, assay, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6 complex (NGFR-BDNF-SORT1-TRAF6) → proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF complex (NGFR-BDNF-SORT1-TRAF6-ZNF274) (modification, collaborate)
    Evidence: mutant phenotype, assay, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NRIF (ZNF274) → proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF complex (NGFR-BDNF-SORT1-TRAF6-ZNF274) (modification, collaborate)
    Evidence: mutant phenotype, assay, other species
  • NCI Pathway Database p75(NTR)-mediated signaling: NRIF (ZNF274) → proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF complex (NGF-NGFR-SORT1-TRAF6-ZNF274) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database p75(NTR)-mediated signaling: NRIF (ZNF274) → proNGF (dimer)/p75(NTR)/Sortilin/TRAF6 complex (NGF-NGFR-SORT1-TRAF6) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database p75(NTR)-mediated signaling: proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF complex (NGF-NGFR-SORT1-TRAF6-ZNF274) → proNGF (dimer)/p75(NTR)/Sortilin/TRAF6 complex (NGF-NGFR-SORT1-TRAF6) (modification, collaborate)
    Evidence: assay, physical interaction
  • Reactome Reaction: NGF → ITGB3BP (indirect_complex)
  • Reactome Reaction: NGF → TRAF6 (indirect_complex)
  • Reactome Reaction: TRAF6 → ITGB3BP (reaction)
  • Reactome Reaction: TRAF6 → ITGB3BP (indirect_complex)
  • Reactome Reaction: NGF → TRAF6 (reaction)
  • Reactome Reaction: NGFR → TRAF6 (indirect_complex)
  • Reactome Reaction: NGFR → ITGB3BP (indirect_complex)
  • Reactome Reaction: NGFR → TRAF6 (reaction)
In total, 44 gene pairs are associated to this article in curated databases