Abstract
Inositol trisphosphate receptor (IP(3)R) mediated Ca(+2) signaling is essential in determining the cell fate by regulating numerous cellular processes, including cell division and cell death. Despite extensive studies about the characterization of IP(3)R in cancer, the underlying molecular mechanism initiating the cell proliferation and apoptosis remained enigmatic. Moreover, in cancer, the modulation of IP(3)R in downstream signaling pathways, which control oncogenesis and cancer progression, is not well characterized. Here, we constructed a biological regulatory network (BRN), and describe the remodeling of IP(3)R mediated Ca(2+) signaling as a central key that controls the cellular processes in cancer. Moreover, we summarize how the inhibition of IP(3)R affects the deregulated cell proliferation and cell death in cancer cells and results in the initiation of pro-survival responses in resistance of cell death in normal cells. Further, we also investigated the role of stereo-specificity of IP(3) molecule and its analogs in binding with the IP(3) receptor. Molecular docking simulations showed that the hydroxyl group at R(6) position along with the phosphate group at R(5) position in 'R' conformation is more favorable for IP(3) interactions. Additionally, Arg-266 and Arg-510 showed π-π and hydrogen bond interactions and Ser-278 forms hydrogen bond interactions with the IP(3) binding site. Thus, they are identified as crucial for the binding of antagonists.