Direct association of presenilin-1 with beta-catenin.
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.
Murayama
M
M
Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, Saitama, Japan.
Tanaka
S
S
Palacino
J
J
Murayama
O
O
Honda
T
T
Sun
X
X
Yasutake
K
K
Nihonmatsu
N
N
Wolozin
B
B
Takashima
A
A
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
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