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Article

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype.

Proceedings of the National Academy of Sciences of the United States of America - 29 Oct 2002

Rozmahel Richard, Mount Howard T J, Chen Fusheng, Nguyen Van, Huang Jean, Erdebil Serap, Liauw Jennifer, Yu Gang, Hasegawa Hiroshe, Gu YongJun, Song You-Qiang, Schmidt Stephen D, Nixon Ralph A, Mathews Paul M, Bergeron Catherine, Fraser Paul, Westaway David, St George-Hyslop Peter

Abstract excerpt

Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the...

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Source

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Identifiers

PMID: 12388777
DOI: 10.1073/pnas.222413999
PMCID: PMC137904

Genes

APP

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

Related research

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Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype.PMID 12388777Read ↗

The presenilins.Semantic proximity Read ↗

Positive and negative regulation of the gamma-secretase activity by nicastrin in a murine model.Semantic proximity Read ↗

Mutations in nicastrin protein differentially affect amyloid beta-peptide production and Notch protein processing.Semantic proximity Read ↗

Drosophila nicastrin is essential for the intramembranous cleavage of notch.Semantic proximity Read ↗

Mutation analysis of the presenilin 1 N-terminal domain reveals a broad spectrum of gamma-secretase activity toward amyloid precursor protein and other substrates.Semantic proximity Read ↗

Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila.Semantic proximity Read ↗

Nicastrin is required for assembly of presenilin/gamma-secretase complexes to mediate Notch signaling and for processing and trafficking of beta-amyloid precursor protein in mammals.Semantic proximity Read ↗

Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.Semantic proximity Read ↗

Role of presenilin in gamma-secretase cleavage of amyloid precursor protein.Semantic proximity Read ↗

Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers.Semantic proximity Read ↗

Nicastrin binds to membrane-tethered Notch.Semantic proximity Read ↗

Function and Dysfunction of PresenilinSemantic proximity Read ↗

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