Yin X M
Department of Pathology, University of Pittsburgh School of Medicine, PA 15261, USA.
Cell Res. 2000 Sep;10(3):161-7. doi: 10.1038/sj.cr.7290045.
Two major apoptosis pathways have been defined in mammalian cells, the Fas/TNF-R1 death receptor pathway and the mitochondria pathway. The Bcl-2 family proteins consist of both anti-apoptosis and pro-apoptosis members that regulate apoptosis, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by caspase 8 in response to Fas/TNF-R1 death receptor signals. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates downstream caspases. Such a connection between the two apoptosis pathways could be important for induction of apoptosis in certain types of cells and responsible for the pathogenesis of a number of human diseases.
在哺乳动物细胞中已确定了两条主要的凋亡途径，即Fas/TNF-R1死亡受体途径和线粒体途径。Bcl-2家族蛋白由抗凋亡和促凋亡成员组成，它们主要通过控制细胞色素c的释放和其他线粒体凋亡事件来调节凋亡。然而，由Fas/TNF-R1受体介导的死亡信号通常可以直接激活半胱天冬酶，绕过对线粒体的需求并逃避Bcl-2家族蛋白的调节。Bid是一种新型的促凋亡Bcl-2家族蛋白，它在响应Fas/TNF-R1死亡受体信号时被半胱天冬酶8激活。活化的Bid转移至线粒体并诱导细胞色素c释放，进而激活下游半胱天冬酶。两条凋亡途径之间的这种联系对于某些类型细胞中凋亡的诱导可能很重要，并与多种人类疾病的发病机制有关。
