STANDARD_NAME	BIOCARTA_PS1_PATHWAY
SYSTEMATIC_NAME	MM1459
COLLECTION	M2:CP:BIOCARTA
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/mouse/geneset/BIOCARTA_PS1_PATHWAY
NAMESPACE	MOUSE_SEQ_ACCESSION
DESCRIPTION_BRIEF	Presenilin action in Notch and Wnt signaling
DESCRIPTION_FULL	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 doman (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.
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CONTRIBUTOR	BioCarta
CONTRIBUTOR_ORG	BioCarta
EXACT_SOURCE	
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EXTERNAL_DETAILS_URL	https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/mouse/m_ps1Pathway.gif
SOURCE_MEMBERS	AK036548,BY107008,NM_001080928,NM_001159598,NM_001165902,NM_007462,NM_007865,NM_008714,NM_008943,NM_009327,NM_009615,NM_009771,NM_010091,NM_019827,NM_021279,NM_021457
GENE_SYMBOLS	Btrc,Rbpj,Rbpj,Axin1,Ctnnb1,Apc,Dll1,Notch1,Psen1,Hnf1a,Adam17,Btrc,Dvl1,Gsk3b,Wnt1,Fzd1
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