Bcl—2家族蛋白与细胞凋亡

Bcl 2家族蛋白是在细胞凋亡过程中起关键性作用的一类蛋白质。在线粒体上 ,Bcl 2家族蛋白通过与其他凋亡蛋白的协同作用 ,调控线粒体结构与功能的稳定性 ,发挥着细胞凋亡“主开关”的作用。Bcl 2家族包括两类蛋白质 :一类是抗凋亡蛋白 ,另一类是促凋亡蛋白。在细胞凋亡时 ,Bcl 2家族中的促凋亡蛋白成员发生蛋白质的加工修饰 ,易位到线粒体的外膜上 ,引起细胞色素c、凋亡诱导因子等其他促凋亡因子的释放 ,导致细胞凋亡 ;而平时被隔离在线粒体等细胞器内的该家族的抗凋亡蛋白成员则抑制细胞色素c和凋亡诱导因子等促凋亡因子的释放 ,具有抑制细胞凋亡的功能。但一旦这类抗凋亡蛋白成员与激活的促凋亡蛋白发生相互作用后 ,便丧失了对细胞凋亡的抑制作用 ,造成线粒体等细胞器的功能丧失和细胞器内促凋亡因子的释放 ,导致细胞凋亡。现以Bcl 2家族调控细胞凋亡的最新研究进展为基础 ,对Bcl 2家族成员及其蛋白质结构、分布和调控细胞凋亡的分子机制进行综述。

Bcl-2 Family Proteins and Apoptosis

Bcl 2 family proteins play key roles in apoptosis. They coordinate with other apoptotic proteins in apoptosis to control mitochondria stability both in structure and function, while mitochondria probably act as the main switch of apoptosis. Bcl 2 family proteins can be divided into two types, anti apoptotic proteins and pro apoptotic proteins. During apoptosis, Bcl 2 family pro apoptotic proteins can translocate to the outer membrane of mitochondrion after posttranslational modification by certain proteases such as caspases. Then cytochrome c (cyt. c ), apoptosis inducing factors (AIFs), and other pro apoptotic factors are released from mitochondrion, triggering apoptosis. Bcl 2 family anti apoptotic proteins sequestered in mitochondrion have ability to inhibit the release of cyt. c and AIFs, and prevent apoptosis. When interacting with activated pro apoptotic proteins, the anti apoptotic proteins lose inhibiting ability of pro apoptotic factors' release, and again triggering apoptosis. Based on the newest research evolvements, types, structures, localizations, apoptosis regulating mechanisms of Bcl 2 family proteins are reviewed.