Abstract:
Programmed cell death via the both intrinsic and extrinsic pathways is regulated by interactions of the Bcl-2 family protein members that determine whether the cell commits to apoptosis via mitochondrial outer membrane permeabilization (MOMP). Recently the conserved C-terminal sequences (CTSs) that mediate localization of Bcl-2 family proteins to intracellular membranes, have been shown to have additional protein-protein binding functions that contribute to the functions of these proteins in regulating MOMP. Here we review the pivotal role of CTSs in Bcl-2 family interactions including: (1) homotypic interactions between the pro-apoptotic executioner proteins that cause MOMP, (2) heterotypic interactions between pro-apoptotic and anti-apoptotic proteins that prevent MOMP, and (3) heterotypic interactions between the pro-apoptotic executioner proteins and the pro-apoptotic direct activator proteins that promote MOMP.
摘要:
通过内在和外在途径的程序性细胞死亡由Bcl-2家族蛋白成员的相互作用调节,所述相互作用决定细胞是否通过线粒体外膜透化(MOMP)进行凋亡。最近,保守的C端序列(CTSs)介导Bcl-2家族蛋白定位到细胞内膜,已显示具有其他蛋白质-蛋白质结合功能,这些功能有助于这些蛋白质调节MOMP。在这里,我们回顾了CTSs在Bcl-2家族相互作用中的关键作用,包括:(1)引起MOMP的促凋亡execution子蛋白之间的同型相互作用,(2)防止MOMP的促凋亡和抗凋亡蛋白之间的异型相互作用,和(3)促凋亡执行者蛋白和促进MOMP的促凋亡直接激活蛋白之间的异型相互作用。