Regulation of Calcium Fluxes and Apoptosis by BCL-2 Family Proteins in Prostate Cancer Cells

摘要

BCL-2 family proteins regulate apoptosis but their mechanisms of action remain unclear. We have demonstrated that Bax and Bak, two pro-apoptotic members of the family, are both capable of triggering release of Ca2+ from the endoplasmic reticulum and that this contributes to cell death in human prostate cancer cells. In work supported by this proposal we performed comprehensive analyses of the effects of siRNA-mediated knockdown of BH3- only members of the family, Bax, and Bak on apoptosis induced by diverse stimuli. The data demonstrate that Bax and Bak play non-overlapping roles in cell death; Bax appears to be linked more closely to cell death induced by stimuli that mobilize ER Ca2+, whereas Bak appears to play a more dominant role in ER stress. In ongoing studies we are assessing the effects of knockdown on ER Ca2+ fluxes and plan to finish the project within a year.