Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071

Alzheimer's disease-related presenilins are thought to be involved in Notch signaling during embryonic development and/or cellular differentiation. Pr oteins mediating the cellular functions of the presenilins are still unknow n. We utilized the yeast two-hybrid system to identify an interacting armad illo protein, termed p0071, that binds specifically to the hydrophilic loop of presenilin 1. In vivo, the presenilins constitutively undergo proteolyt ic processing, forming two stable fragments. Here, we show that the C-termi nal fragment of presenilin 1 directly binds to p0071. Nine out of 10 armadi llo repeats in p0071 are essential for mediating this interaction. Since ar madillo proteins, like beta-catenin and APC, are known to participate in ce llular signaling, p0071 may function as a mediator of presenilin 1 in signa ling events.