title: Direct association of presenilin-1 with beta-catenin.
abstract: Families bearing mutations in the presenilin-1 (PSI) gene develop Alzheimer's disease (AD). However, the mechanism through which PS1 causes AD is unclear. The co-immunoprecipitation with PS1 in transfected COS-7 cells indicates that PSI directly interacts with endogenous beta-catenin, and the interaction requires residues 322450 of PSI and 445-676 of beta-catenin. Both proteins are co-localized in the endoplasmic reticulum. Over-expression of PS1 reduces the level of cytoplasmic beta-catenin, and inhibits beta-catenin-T cell factor-regulated transcription. These results indicate that PSI plays a role as inhibitor of the beta-catenin signal, which may be connected with the AD dysfunction.
authors.affiliation: Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murayama
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Palacino
authors.forename: O
authors.initials: O
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: K
authors.initials: K
authors.lastname: Yasutake
authors.forename: N
authors.initials: N
authors.lastname: Nihonmatsu
authors.forename: B
authors.initials: B
authors.lastname: Wolozin
authors.forename: A
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000544:Alzheimer Disease; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007163:Immunosorbent Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009447:Neuroblastoma / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D053764:Presenilin-1; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D015534:Trans-Activators; D051176:beta Catenin