文摘
Presenilins (PS) are involved in γ-secretase-mediated processing of β-amyloid precursor protein (APP) and the Notch family of proteins. In addition, presenilin 1 (PS-1) binds to members of the armadillo family of proteins. In this study the relationship between PS-1-mediated proteolytic activity and PS-1-mediated regulation of β-catenin function was investigated. Incubation of cells with a potent, small molecule γ-secretase inhibitor did not affect PS-1/β-catenin interaction as determined by co-immunoprecipitation, or affect the regulation of β-catenin turnover, as determined by pulse-chase analysis, even at inhibitor concentrations that completely blocked PS-mediated APP processing. Moreover, inhibition of PS-1-mediated proteolytic activity did not affect β-catenin trafficking, as determined by immunolocalization and immunoblotting, or β-catenin-mediated transcription. These results indicate that PS-1-mediated regulation of γ-secretase activity and PS-1-mediated regulation of β-catenin function can be pharmacologically separated and support the idea that these are distinct functions.