DIRECT ASSOCIATION OF PRESENILIN-1 WITH BETA-CATENIN

Families bearing mutations in the presenilin-1 (PS1) gene develop Alzh eimer'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 beta-cat enin, and the interaction requires residues 322-450 of PS1 and 445-676 of beta-catenin, Both proteins are co-localized in the endoplasmic re ticulum, Over-expression of PS1 reduces the level of cytoplasmic beta- catenin, and inhibits beta-catenin-T cell factor-regulated transcripti on, These results indicate that PS1 plays a role as inhibitor of the b eta-catenin signal, which may be connected with the AD dysfunction, (C ) 1998 Federation of European Biochemical Societies.