Direct association of presenilin‐1 with β‐catenin

FEBS Letters

Nihonmatsu, Naomi³  Yasutake, Kaori²  Sun, Xiaoyan³  Honda, Toshiyuki³  Wolozin, Benjamin¹  Palacino, James¹  Takashima, Akihiko³  Tanaka, Shoji²  Murayama, Miyuki³  Murayama, Ohoshi³ 

[1] Department of Pharmacology, Loyola University Medical Center, 2160 South First Ave., Maywood, IL 60153, USA;Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida-shi, Tokyo 194, Japan;Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, 2–1 Hirosawa, Wako-shi, Saitama 351–0198, Japan

关键词: Presenilin-1;    β-Catenin;    Glycogen synthase kinase 3β;    Alzheimer's disease;    PS1;    presenilin 1;    AD;    Alzheimer's disease;    ER;    endoplasmic reticulum;    Tcf;    T cell factor;    Aβ;    amyloid β protein;   

DOI  :  10.1016/S0014-5793(98)00886-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Families bearing mutations in the presenilin-1 (PS1) 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 PS1 directly interacts with endogenous β-catenin, and the interaction requires residues 322–450 of PS1 and 445–676 of β-catenin. Both proteins are co-localized in the endoplasmic reticulum. Over-expression of PS1 reduces the level of cytoplasmic β-catenin, and inhibits β-catenin-T cell factor-regulated transcription. These results indicate that PS1 plays a role as inhibitor of the β-catenin signal, which may be connected with the AD dysfunction.

【 授权许可】

Unknown