TY - JOUR
T1 - The presenilin-2 loop peptide perturbs intracellular Ca2+ homeostasis and accelerates apoptosis
AU - Cai, Chuanxi
AU - Lin, Peihui
AU - CHEUNG, King-Ho
AU - Li, Na
AU - Levchook, Christina
AU - Pan, Zui
AU - Ferrante, Christopher
AU - Boulianne, Gabrielle L.
AU - Foskett, J. Kevin
AU - Danielpour, David
AU - Ma, Jianjie
N1 - This work was supported by Grants R01-CA95379, R01-A1555G, R01-HL69000 (to J. M.), and R01-GM056328 (to J. K. F.) from the National Institutes of Health and a UMDNJ Foundation Research grant (to Z. P.). The costs of publication of this article were defrayed in part by the payment of page charges.
PY - 2006/6
Y1 - 2006/6
N2 - In cells undergoing apoptosis, a 22-amino-acid presenilin-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 Ca(2+) release from the endoplasmic reticulum. These results indicate that PS2-LP-mediated alteration of intracellular Ca(2+) 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.
AB - In cells undergoing apoptosis, a 22-amino-acid presenilin-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 Ca(2+) release from the endoplasmic reticulum. These results indicate that PS2-LP-mediated alteration of intracellular Ca(2+) 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.
U2 - 10.1074/jbc.M512026200
DO - 10.1074/jbc.M512026200
M3 - Journal article
SN - 0021-9258
VL - 281
SP - 16649
EP - 16655
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -
