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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Mm" NAME="export">
    <GENESET STANDARD_NAME="BIOCARTA_PS1_PATHWAY" SYSTEMATIC_NAME="MM1459" HISTORICAL_NAMES="" PMID="" AUTHORS="" GEOID="" EXACT_SOURCE="" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/mouse/m_ps1Pathway.gif" CHIP="MOUSE_SEQ_ACCESSION" CONTRIBUTOR="BioCarta" CONTRIBUTOR_ORG="BioCarta" 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." TAGS="" 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" MEMBERS_SYMBOLIZED="Adam17,Apc,Axin1,Btrc,Ctnnb1,Dll1,Dvl1,Fzd1,Gsk3b,Hnf1a,Notch1,Psen1,Rbpj,Wnt1" MEMBERS_EZID="11491,11789,12005,12234,12387,13388,13542,14362,18128,19164,19664,21405,22408,56637" MEMBERS_MAPPING="AK036548,Btrc,12234|BY107008,Rbpj,19664|NM_001080928,Rbpj,19664|NM_001159598,Axin1,12005|NM_001165902,Ctnnb1,12387|NM_007462,Apc,11789|NM_007865,Dll1,13388|NM_008714,Notch1,18128|NM_008943,Psen1,19164|NM_009327,Hnf1a,21405|NM_009615,Adam17,11491|NM_009771,Btrc,12234|NM_010091,Dvl1,13542|NM_019827,Gsk3b,56637|NM_021279,Wnt1,22408|NM_021457,Fzd1,14362" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="M2" ORGANISM="Mus musculus" SUB_CATEGORY_CODE="CP:BIOCARTA"/>
</MSIGDB>
