Bcl-2 is a member of a family of proteins that regulate cell survival. Expression of Bcl-2 is aberrantly elevated in many types of cancer. Within cells of the immune system, Bcl-2 has a physiological role in regulating immune responses. However, in cancers arising from cells of the immune system Bcl-2 promotes cell survival and proliferation. This review summarizes discoveries over the past 30 years that have elucidated Bcl-2's role in the normal immune system, including its actions in regulating calcium (Ca2+) signals necessary for the immune response, and for Ca2+-mediated apoptosis at the end of an immune response. How Bcl-2 modulates the release of Ca2+ from intracellular stores via inositol 1,4,5-trisphosphate receptors (IP3R) is discussed, and in particular, the role of Bcl-2/IP3R interactions in promoting the survival of cancer cells by preventing Ca2+-mediated cell death. The development and usage of a peptide, referred to as TAT-Pep8, or more recently, BIRD-2, that induces death of cancer cells by inhibiting Bcl-2's control over IP3R-mediated Ca2+ elevation is discussed. Studies aimed at discovering a small molecule that mimics BIRD-2's anticancer mechanism of action are summarized, along with the prospect of such a compound becoming a novel therapeutic option for cancer.

中文翻译：

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通过靶向 Bcl-2 和 IP3 受体之间的相互作用创造一种新的癌症治疗剂。

Bcl-2 是调节细胞存活的蛋白质家族的成员。Bcl-2 的表达在许多类型的癌症中异常升高。在免疫系统的细胞内，Bcl-2 在调节免疫反应方面具有生理作用。然而，在由免疫系统细胞引起的癌症中，Bcl-2 促进细胞存活和增殖。本综述总结了过去 30 年来阐明 Bcl-2 在正常免疫系统中的作用的发现，包括其在调节免疫反应所需的钙 (Ca2+) 信号和免疫结束时 Ca2+ 介导的细胞凋亡中的作用。回复。讨论了 Bcl-2 如何通过肌醇 1,4,5-三磷酸受体 (IP3R) 从细胞内储存中调节 Ca2+ 的释放，特别是，Bcl-2/IP3R 相互作用通过阻止 Ca2+ 介导的细胞死亡来促进癌细胞存活的作用。讨论了一种称为 TAT-Pep8 或最近称为 BIRD-2 的肽的开发和使用，该肽通过抑制 Bcl-2 对 IP3R 介导的 Ca2+ 升高的控制来诱导癌细胞死亡。总结了旨在发现模拟 BIRD-2 抗癌作用机制的小分子的研究，以及这种化合物成为癌症新治疗选择的前景。