γ-Secretase activity is not involved in presenilin-mediated regulation of β-catenin

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• 作者：Meredith Jr ; Jere E. ; Wang ; Qian ; Mitchell ; Thomas J. ; Olson ; Richard E. ; Zaczek ; Robert ; Stern ; Andrew M. ; et. al.
• 关键词：Presenilin ; γ ; -Secretase ; β ; -Amyloid precursor protein ; β ; -Catenin ; Alzheimer’ ; s disease
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2002
• 出版时间：December 20, 2002
• 年：2002
• 卷：299
• 期：5
• 页码：744-750
• 全文大小：281 K

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.