The presenilin-2 loop peptide perturbs intracellular Ca2+ homeostasis and accelerates apoptosis

被引：35
作者：
Cai, Chuanxi
Lin, Peihui
Cheung, King-Ho
Li, Na
Levchook, Christina
Pan, Zui
Ferrante, Christopher
Boulianne, Gabrielle L.
Foskett, J. Kevin
Danielpour, David
Ma, Jianjie
机构：
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA
[2] Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada
[3] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA
[4] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2006年 / 281卷 / 24期
关键词：
D O I：
10.1074/jbc.M512026200
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In cells undergoing apoptosis, a 22-amino-acidpresenilin-2-loop peptide (PS2-LP, amino acids 308-329 in presenilin-2) is generated through cleavage of the carboxyl-terminal fragment of presenilin- 2 by caspase-3. The impact of PS2-LP on the progression of apoptosis, however, is not known. Here we show that PS2-LP is a potent inducer of the mitochondrial-dependent cell death pathway when transduced as a fusion protein with HIV-TAT. Biochemical and functional studies demonstrate that TAT-PS2-LP can interact with the inositol 1,4,5-trisphosphate receptor and activate Ca2(+) release from the endoplasmic reticulum. These results indicate that PS2LP-mediated alteration of intracellular Ca2(+) homeostasis may be linked to the acceleration of apoptosis. Therefore, targeting the function of PS2-LP could provide a useful therapeutic tool for the treatment of cancer and degenerative diseases.
引用
收藏
页码：16649 / 16655
页数：7
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