{"doi":"10.1074/jbc.m308480200","title":"Notch1 Competes with the Amyloid Precursor Protein for γ-Secretase and Down-regulates Presenilin-1 Gene Expression","abstract":null,"journal":"Journal of Biological Chemistry","year":2003,"id":603687,"datarank":0.6038027536102726,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":0.0,"self_endowment_contribution":0.6038027536102726,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367419,"name":"Oksana Berezovska","orcid":"0000-0003-4898-5788","position":1,"is_corresponding":false},{"id":1548650,"name":"Pavan Ramdya","orcid":null,"position":2,"is_corresponding":false},{"id":1548652,"name":"Hiroaki Fukumoto","orcid":null,"position":3,"is_corresponding":false},{"id":1548653,"name":"Susan Raju","orcid":null,"position":4,"is_corresponding":false},{"id":1548655,"name":"Tejal Shah","orcid":null,"position":5,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":6,"is_corresponding":false},{"id":27613,"name":"Alberto Lleó","orcid":"0000-0002-2568-5478","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Notch1 Competes with the Amyloid Precursor Protein for γ-Secretase and Down-regulates Presenilin-1 Gene Expression","abstract":"Presenilin 1 (PS1) is a critical component of the gamma-secretase complex, which is involved in the cleavage of several substrates including the amyloid precursor protein (APP) and Notch1. Based on the fact that APP and Notch are processed by the same gamma-secretase, we postulated that APP and Notch compete for the enzyme activity. In this report, we examined the interactions between APP, Notch, and PS1 using the direct gamma-secretase substrates, Notch 1 Delta extracellular domain (N1DeltaEC) and APP carboxyl-terminal fragment of 99 amino acids, and measured the effects on amyloid-beta protein production and Notch signaling, respectively. Additionally, we tested the hypothesis that downstream effects on PS1 expression may coexist with the competition phenomenon. We observed significant competition between Notch and APP for gamma-secretase activity; transfection with either of two direct substrates of gamma-secretase led to a reduction in the gamma-cleaved products, Notch intracellular domain or amyloid-beta protein. In addition, however, we found that activation of the Notch signaling pathway, by either N1 Delta EC or Notch intracellular domain, induced down-regulation of PS1 gene expression. This finding suggests that Notch activation directly engages gamma-secretase and subsequently leads to diminished PS1 expression, suggesting a complex set of feedback interactions following Notch activation.","is_dataset_classified":null,"base_score":4.02535169073515,"endowment":4.02535169073515,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12960155","pmcid":null,"openalex_id":"https://openalex.org/W2120860069","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"AG15379","title":null}],"total_grants":1,"fwci":3.0779,"citation_percentile":0.91632772,"influential_citations":0,"citation_trend":[{"year":2013,"count":5},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":3},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1074/jbc.m308480200","host_type":"journal"},{"url":"https://doi.org/10.1074/jbc.m308480200","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820757571?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820757571?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M308480200","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12960155","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Hedgehog Signaling Pathway Studies","Prion Diseases and Protein Misfolding"],"mesh_terms":["Animals","beta-Galactosidase","Binding, Competitive","Cell Line","Enzyme-Linked Immunosorbent Assay","Humans","Luciferases","Membrane Proteins","Endopeptidases","Plasmids","Protein Binding","Receptors, Cell Surface","Transcription Factors","Transfection","Blotting, Western","Signal Transduction","Down-Regulation","Aspartic Acid Endopeptidases","Amyloid beta-Protein Precursor","Protein Structure, Tertiary","Reverse Transcriptase Polymerase Chain Reaction","Feedback, Physiological","Cell Line, Tumor","Mice","Receptor, Notch1","Presenilin-1","Amyloid Precursor Protein Secretases"],"keywords":["Presenilin","Notch signaling pathway","Amyloid precursor protein secretase","Amyloid precursor protein","Intracellular","Cell biology","Alpha secretase","Notch proteins","Notch 1","Chemistry","Extracellular","Signal transduction","Biochemistry","Biology","Alzheimer's disease","Internal medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T22:30:17.054958Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}