In this review we speculate that the anti-apoptotic protein Bcl-2 may regulate calcium signals involved in mediating cell death. Evidence that Ins(1,4,5)P3-mediated calcium release from the endoplasmic reticulum triggers apoptosis in response to diverse signals is summarized. Also, we review evidence that Bcl-2 regulates calcium release from the endoplasmic reticulum, and speculate that Bcl-2 may interact either functionally or physically with Ins(1,4,5)P3 receptors to modulate calcium signals that determine life or death decisions.

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