Rong Yiping, Distelhorst Clark W
Department of Medicine and Pharmacology, Comprehensive Cancer Center and University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA.
Annu Rev Physiol. 2008;70:73-91. doi: 10.1146/annurev.physiol.70.021507.105852.
Bcl-2 family members are important regulators of cell survival and cell death. Researchers have focused mainly on mitochondria, where both proapoptotic and antiapoptotic family members function to regulate the release of cytochrome c and other mediators of apoptosis. However, as reviewed here, Bcl-2 family members also operate on another front, the endoplasmic reticulum (ER), to both positively and negatively regulate the release of Ca2+. There is abundant evidence that Ca2+ signals trigger apoptosis in response to a wide variety of agents and conditions. Conversely, Ca2+ signals can also mediate cell survival. Recent findings indicate that Bcl-2 interacts with inositol 1,4,5-trisphosphate (IP3) receptor Ca2+ channels on the ER, regulating their opening in response to IP3- and thus inhibiting IP3-mediated Ca2+ signals that induce apoptosis while enhancing Ca2+ signals that support cell survival.
Bcl-2家族成员是细胞存活和细胞死亡的重要调节因子。研究人员主要关注线粒体，促凋亡和抗凋亡家族成员都在其中发挥作用，调节细胞色素c和其他凋亡介质的释放。然而，如本文所述，Bcl-2家族成员还在另一个层面发挥作用，即内质网（ER），对Ca2+的释放进行正向和负向调节。有充分证据表明，Ca2+信号在多种因素和条件下会触发细胞凋亡。相反，Ca2+信号也可以介导细胞存活。最近的研究结果表明，Bcl-2与内质网上的肌醇1,4,5-三磷酸（IP3）受体Ca2+通道相互作用，调节其对IP3的响应开放，从而抑制诱导细胞凋亡的IP3介导的Ca2+信号，同时增强支持细胞存活的Ca2+信号。
