The Bcl-2 protein, best known for its ability to inhibit apoptosis, interacts with the inositol 1,4,5-trisphosphate receptor (IP(3)R) Ca(2+) channel to regulate IP(3)-mediated Ca(2+) release from the endoplasmic reticulum. This review summarizes the current state of knowledge regarding the interaction of Bcl-2, and also its homologue Bcl-xl, with the IP(3)R and how these interactions regulate Ca(2+) signaling. The dual role of these interactions in promoting prosurvival Ca(2+) signals, while at the same time inhibiting proapoptotic Ca(2+) signals, is discussed. Moreover, this review will elucidate the recently recognized importance of the Bcl-2-IP(3)R interaction in human disease.
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