Murayama M, Tanaka S, Palacino J, Murayama O, Honda T, Sun X, Yasutake K, Nihonmatsu N, Wolozin B, Takashima A
Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, Saitama, Japan.
FEBS Lett. 1998 Aug 14;433(1-2):73-7. doi: 10.1016/s0014-5793(98)00886-2.
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.
携带早老素-1（PSI）基因突变的家族会患阿尔茨海默病（AD）。然而，PSI导致AD的机制尚不清楚。在转染的COS-7细胞中与PSI进行的免疫共沉淀表明，PSI与内源性β-连环蛋白直接相互作用，这种相互作用需要PSI的322-450位残基和β-连环蛋白的445-676位残基。两种蛋白都在内质网中共定位。PSI的过表达降低了细胞质β-连环蛋白的水平，并抑制β-连环蛋白-T细胞因子调节的转录。这些结果表明，PSI作为β-连环蛋白信号的抑制剂发挥作用，这可能与AD功能障碍有关。
