Article

The amino-terminal peptide of Bax perturbs intracellular Ca2+ homeostasis to enhance apoptosis in prostate cancer cells.

Dept. of Physiology and Biophysics, and Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
AJP Cell Physiology (impact factor: 3.54). 01/2009; 296(2):C267-72. DOI:10.1152/ajpcell.00390.2008 pp.C267-72
Source: PubMed

ABSTRACT During apoptosis, proteolytic cleavage of Bax at the amino terminus generates a truncated Bax of approximately 18 kDa (p18Bax) and an amino-terminal peptide of approximately 3 kDa (p3Bax). Whereas extensive studies have shown that p18Bax behaves like a BH3 protein with enhanced pro-apoptotic function over that of the full-length Bax (p21Bax), little is known about the function of p3Bax in apoptosis. We have previously shown that Bax and Ca2+ play a synergistic role in amplifying apoptosis signaling and that store-operated Ca2+ entry (SOCE) contributes to Bax-mediated apoptosis in prostate cancer cells. Here we test whether p3Bax can contribute to regulation of Ca2+ signaling during apoptosis through use of a membrane-penetrating peptide to facilitate delivery of recombinant p3Bax into NRP-154 cells, a prostate epithelial cell line with tumorigenic capacity. We find that human immunodefficiency virus transactivator of transcription protein (TAT)-p3Bax fusion peptide can enhance thapsigargin-induced apoptosis in NRP-154 cells, elevate SOCE activity, and increase inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores. Our data indicates that p3Bax can modulate the entry of extracellular Ca2+ and thus regulate the amplification of apoptosis in prostate cancer cells.

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    Article: Delivery of intracellular-acting biologics in pro-apoptotic therapies.
    Hongmei Li, Chris E Nelson, Brian C Evans, Craig L Duvall
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    Current pharmaceutical design 02/2011; 17(3):293-319. · 4.41 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

amino-terminal peptide
 
amplifying apoptosis signaling
 
Bax-mediated apoptosis
 
Ca2+ signaling
 
elevate SOCE activity
 
full-length Bax
 
human immunodefficiency virus transactivator
 
membrane-penetrating peptide
 
NRP-154 cells
 
p18Bax behaves
 
p3Bax
 
prostate cancer cells
 
prostate epithelial cell line
 
recombinant p3Bax
 
store-operated Ca2+ entry
 
synergistic role
 
TAT)-p3Bax fusion peptide
 
thapsigargin-induced apoptosis
 
truncated Bax
 
tumorigenic capacity