The amino-terminal peptide of Bax perturbs intracellular Ca2+ homeostasis to enhance apoptosis in prostate cancer cells.
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.
Li
Na
N
Dept. of Physiology and Biophysics, and Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Lin
Peihui
P
Cai
Chuanxi
C
Pan
Zui
Z
Weisleder
Noah
N
Ma
Jianjie
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics
C494827:Bax protein, mouse; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium