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NOTCH2 intracellular domain regulates transcription

Source
Taxonomic Scope
organism_specific
Category
pathway
Dates
  • Create:
    2019-01-17
  • Modify:
    2025-02-01
Description
In the nucleus, NICD2 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind). NICD2:RBPJ:MAML complex activates transcription from RBPJ-binding promoter elements (RBEs) (Wu et al. 2000). Besides NICD2, RBPJ and MAML, NOTCH2 coactivator complex likely includes other proteins, shown as components of the NOTCH1 coactivator complex. NOTCH2 coactivator complex directly stimulates transcription of HES1 and HES5 genes (Shimizu et al. 2002), both of which are known NOTCH1 targets. The promoter of FCER2 (CD23A) contains several RBEs that are occupied by NOTCH2 but not NOTCH1 coactivator complexes, and NOTCH2 activation stimulates FCER2 transcription. Overexpression of FCER2 (CD23A) is a hallmark of B-cell chronic lymphocytic leukemia (B-CLL) and correlates with the malfunction of apoptosis, which is thought be an underlying mechanism of B-CLL development. The Epstein-Barr virus protein EBNA2 can also activate FCER2 transcription through RBEs, possibly by mimicking NOTCH2 signaling (Hubmann et al. 2002). NOTCH2 coactivator complex occupies the proximal RBE of the GZMB (granzyme B) promoter and at the same time interacts with phosphorylated CREB1, bound to an adjacent CRE site. EP300 transcriptional coactivator is also recruited to this complex through association with CREB1 (Maekawa et al. 2008). NOTCH2 coactivator complex together with CREBP1 and EP300 stimulates transcription of GZMB (granzyme B), which is important for the cytotoxic function of CD8+ T-cells (Maekawa et al. 2008). There are indications that NOTCH2 genetically interacts with hepatocyte nuclear factor 1-beta (HNF1B) in kidney development (Massa et al. 2013, Heliot et al. 2013) and with hepatocyte nuclear factor 6 (HNF6) in bile duct formation (Vanderpool et al. 2012), but the exact nature of these genetic interactions has not been defined.

1 Identity

1.1 Source

1.2 External ID

2 Proteins

2.1 GlycoProteins

PubChem Protein
GlycoProtein
PubChem Protein
GlycoProtein
PubChem Protein
GlycoProtein
PubChem Protein
GlycoProtein
PubChem Protein
GlycoProtein
PubChem Protein
GlycoProtein

3 Genes

3.1 GlycoGenes

PubChem Gene
GlycoGene

5 Literature

5.1 Consolidated References

6 Information Sources

  1. Reactome
    LICENSE
    Reactome is an open source and open access resource, available to anyone and covered by two Creative Commons licenses: the terms of the Creative Commons Public Domain (CC0) License apply to all Reactome annotation files, e.g. identifier mapping data, specialized data files, and interaction data derived from Reactome; the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License apply to all software and code, e.g. relating to the functionality of the reactome.org, derived websites and webservices, the Curator Tool, the Functional Interaction application, SQL and Graph Database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials.
    https://reactome.org/license
  2. PubChem
  3. GlyCosmos Glycoscience Portal
    LICENSE
    All copyrightable parts of the datasets in GlyCosmos are under the Creative Commons Attribution (CC BY 4.0) License.
    https://glycosmos.org/license
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