Notch Proteolysis and Signaling Pathway

Preferred Label : Notch Proteolysis and Signaling Pathway;

NCIt synonyms : Notch Signaling Pathway;

NCIt related terms : Proteolysis and Signaling Pathway of Notch;

Alternative definition : BIOCARTA: Notch is a large cell-surface receptor that is activated by contact with membrane-bound ligands on neighboring cells. The ligands that activate Notch include Delta and Serrate, and Lag-2 is a Notch ligand in C. elegans. Activation of Notch by binding with its ligand on the surface of neighboring cells is involved in several developmental pathways, helping to determine cell fate. Much of the early insight into Notch signaling was derived from genetic studies in Drosophila and C. elegans models. Three different proteolytic steps process the 300 kD precursor of mature Notch. One protease is a furin-like enzyme that cleaves Notch constitutively adjacent to the amino acid sequence RQRR in the extracellular domain. Another proteolytic step in Notch processing is carried out by TACE, also known as ADAM17. Binding of extracellular ligand to Notch also induces cleavage at the transmembrane region by a gamma-secretase activity that is dependent on presenilin-1. The exact identity of the polypeptide that catalyzes the gamma-secretase enzyme activity has been debated. Labeling of presenilin with irreversible gamma-secretase transition state inhibitors indicates that is itself in fact the site of protease activity. It has also been argued that the gamma secretase is not presenilin-1 itself, but another polypeptide that requires Notch for its activity and is distinct from Presenilin-1. Cleavage of Notch in the extracellular domain releases the Notch intracellular domain (BIOCARTAD) which migrates into the nucleus where it associates with CSL transcription factors and acts as a transcriptional coactivator. The proteolytic processing of Notch resembles in several ways the proteolytic processing of amyloid precursor protein (APP) that is implicated in plaque formation in Alzheimer's disease, with TACE and Presenilin-1 implicated in proteolytic processing of both Notch and APP. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

NCI Metathesaurus CUI : CL323293;

Biocarta ID : h_notchpathway;

Details

Origin ID

C39170;

UMLS CUI

C1155452;

Automatic exact mappings (from CISMeF team)
- Notch signaling pathway [GO term]
Semantic type(s)
- Molecular Function [UMLS semantic type]
UMLS correspondences (same concept)
- Notch signaling pathway [GO term]
has_gene_product_element
- Delta-Like Protein 4 [NCIt concept]
- Furin [NCIt concept]
- Myc Proto-Oncogene Protein [NCIt concept]
- Neurogenic Locus Notch Homolog Protein 1 [NCIt concept]
- Presenilin-1 [NCIt concept]
- Protein Jagged-1 [NCIt concept]
- Protein Jagged-2 [NCIt concept]
- Recombining Binding Protein Suppressor of Hairless [NCIt concept]
pathway_has_gene_element
- DLL4 wt Allele [NCIt concept]
- FURIN wt Allele [NCIt concept]
- JAG1 wt Allele [NCIt concept]
- JAG2 wt Allele [NCIt concept]
- MYC wt Allele [NCIt concept]
- NOTCH1 wt Allele [NCIt concept]
- PSEN1 wt Allele [NCIt concept]
- RBPJ wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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