Preferred Label : Notch and Wnt Signaling Pathway;
NCIt related terms : Presenilin action in Notch and Wnt signaling;
Alternative definition : BIOCARTA: Presenilin-1 (PS1) is associated with gamma secretase activity that cleaves
amyloid precursor protein (APP) and is implicated in Alzheimer's disease. Presenilin-1
is also a component in gamma-secretase activity involved in signaling by the transmembrane
protein Notch. Active gamma secretase requires PS-1 N-terminal fragment and a C-terminal
fragment and is unique in catalyzing proteolysis within the transmembrane region of
proteins. Other proteins such as nicastrin may also be components of the gamma-secretase.
Binding of the ligand Delta by Notch appears to trigger two proteolytic cleavages
of Notch. The first step cleaves an extracellular domain and is catalyzed by a metalloprotease
termed alpha-secretase or TACE. The second cleavage step appears to occur within the
transmembrane domain of Notch, and releases a Notch intracellular domain (NICD). Once
released, NICD moves into the nucleus where it is involved in transcriptional regulation
through CSL family transcription factors (CBF1, Su(H), Lag-1) or other transcriptional
regulators such as LEF-1. Presenilin is also involved in the Wnt/frizzled signaling
pathway through beta-catenin. Beta-catenin is a cytoskeletal component that enters
the nucleus to act as a transcriptional cofactor. Binding of WNT to Frizzled causes
disheveled (DSH) to inhibit Glycogen synthase kinase 3 beta (GSK-3b) activity. Phosphorylation
of Beta-catenin induces the ubiquitination and proteolytic degradation of beta-catenin
by the proteasome. Non-phosphorylated beta-catenin is stable and enters the nucleus
to regulate transcription with TCF. The beta-catenin/TCF complex activates genes that
promote cellular survival, proliferation and differentiation during development. Presenilin
stimulates beta-catenin turnover, reducing its transcriptional activation. (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may be outdated - see the DesignNote.);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Definition might be outdated or inaccurate.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/.;
Biocarta ID : h_ps1Pathway;
Origin ID : C39202;
UMLS CUI : C1518427;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
