The amino-terminal peptide of Bax perturbs intracellular Ca ²⁺ homeostasis to enhance apoptosis in prostate cancer cells

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 Ca ²⁺ play a synergistic role in amplifying apoptosis signaling and that store-operated ²⁺ entry (SOCE) contributes to Bax-mediated apoptosis in prostate cancer cells. Here we test whether p3Bax can contribute to regulation of ²⁺ 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 intra- cellular ²⁺ stores. Our data indicates that p3Bax can modulate the entry of extracellular ²⁺ and thus regulate the amplification of apoptosis in prostate cancer cells.