About: Notch and Wnt Signaling Pathway

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About: Notch and Wnt Signaling Pathway Goto Sponge NotDistinct Permalink

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Attributes	Values
rdf:type	Class
rdfs:label	Notch and Wnt Signaling Pathway
rdfs:subClassOf	Signaling Pathway
Semantic_Type	Functional Concept
Preferred_Name	Notch and Wnt Signaling Pathway
UMLS_CUI	C1518427
BioCarta_ID	h_ps1Pathway
ALT_DEFINITION	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.BIOCARTA
Legacy_Concept_Name	Notch_and_Wnt_Signaling_Pathway
FULL_SYN	Presenilin action in Notch and Wnt signalingPTBIOCARTA Notch and Wnt Signaling PathwayPTNCI
code	C39202
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