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GROWTH, DIFFERENTIATION, AND APOPTOSIS

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

Department of ¹Physiology and Biophysics, and Department of ²Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey

Submitted 30 July 2008 ; accepted in final form 10 December 2008

During apoptosis, proteolytic cleavage of Bax at the amino terminus generates a truncated Bax of 18 kDa (p18Bax) and an amino-terminal peptide of 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.

human immunodefficiency virus transactivator of transcription protein-p3Bax; transforming growth factor-β; calcium signaling; therapy; thapsigargin