Direct association of presenilin-1 with β-catenin

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 beta-catenin, and the interaction requires residues 322-450 of PS1 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 PS1 plays a role as inhibitor of the beta-catenin signal, which may be connected with the AD dysfunction, (C) 1998 Federation of European Biochemical Societies.