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

Chuanxi Cai, Peihui Lin, King-Ho CHEUNG, Na Li, Christina Levchook, Zui Pan, Christopher Ferrante, Gabrielle L. Boulianne, J. Kevin Foskett, David Danielpour, Jianjie Ma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)16649-55
Number of pages7
JournalJournal of Biological Chemistry
Volume281
Issue number24
DOIs
Publication statusPublished - Jun 2006

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