Gene interactions and pathways from curated databases and text-mining
EMBO J 1999, PMID: 10205173

Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.

Ohtsuka, T; Ishibashi, M; Gradwohl, G; Nakanishi, S; Guillemot, F; Kageyama, R

While the transmembrane protein Notch plays an important role in various aspects of development, and diseases including tumors and neurological disorders, the intracellular pathway of mammalian Notch remains very elusive. To understand the intracellular pathway of mammalian Notch, the role of the bHLH genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologues) was examined by retrovirally misexpressing the constitutively active form of Notch (caNotch) in neural precursor cells prepared from wild-type, Hes1-null, Hes5-null and Hes1-Hes5 double-null mouse embryos. We found that caNotch, which induced the endogenous Hes1 and Hes5 expression, inhibited neuronal differentiation in the wild-type, Hes1-null and Hes5-null background, but not in the Hes1-Hes5 double-null background. These results demonstrate that Hes1 and Hes5 are essential Notch effectors in regulation of mammalian neuronal differentiation.

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Text Mining Data

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Manually curated Databases

  • NCI Pathway Database Notch-mediated HES/HEY network: TWIST1 (TWIST1) → HES1 (HES1) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene
  • NCI Pathway Database Notch-mediated HES/HEY network: TWIST1 (TWIST1) → RBPJ/NICD/MAML1-2/p300 complex (NOTCH1-RBPJ-MAML1_MAML2-EP300) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene
  • NCI Pathway Database Notch-mediated HES/HEY network: RBPJ/NCoR/HDAC1 complex (RBPJ-NCOR1_NCOR2-HDAC1) → HES1 (HES1) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene
  • NCI Pathway Database Notch-mediated HES/HEY network: RBPJ/NCoR/HDAC1 complex (RBPJ-NCOR1_NCOR2-HDAC1) → RBPJ/NICD/MAML1-2/p300 complex (NOTCH1-RBPJ-MAML1_MAML2-EP300) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene
  • NCI Pathway Database Notch-mediated HES/HEY network: HES1 (HES1) → RBPJ/NICD/MAML1-2/p300 complex (NOTCH1-RBPJ-MAML1_MAML2-EP300) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene, physical interaction
  • NCI Pathway Database Notch-mediated HES/HEY network: SHARP/RBPJ complex (SPEN-RBPJ) → RBPJ/NICD/MAML1-2/p300 complex (NOTCH1-RBPJ-MAML1_MAML2-EP300) (transcription, inhibits)
    Evidence: mutant phenotype, reporter gene
In total, 46 gene pairs are associated to this article in curated databases