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NOTCH2 intracellular domain regulates transcription

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-2197563

PubChem

R-HSA-2197563

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.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 10** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P06734	Low affinity immunoglobulin epsilon Fc receptor	CD23A CLEC4J FCE2 FCER2 IGEBF	view
P10144	Granzyme B	CGL1 CSPB CTLA1 GRB GZMB	view
Q04721	Neurogenic locus notch homolog protein 2	NOTCH2	view
Q06330	Recombining binding protein suppressor of hairless	IGKJRB IGKJRB1 RBPJ RBPJK RBPSUH	view
Q09472	Histone acetyltransferase p300	EP300 P300	view
Q13495	Mastermind-like domain-containing protein 1	CG1 CXorf6 MAMLD1	view
Q14469	Transcription factor HES-1	BHLHB39 HES1 HL HRY	view
Q8IZL2	Mastermind-like protein 2	KIAA1819 MAML2	view
Q92585	Mastermind-like protein 1	KIAA0200 MAML1	view
Q96JK9	Mastermind-like protein 3	KIAA1816 MAML3	view

Displaying 1 entry
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_000766	P06734	Low affinity immunoglobulin epsilon Fc receptor	view

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