BCL-2 蛋白与细胞凋亡：最新见解与未解之谜。

BCL-2 proteins and apoptosis: Recent insights and unknowns.

机构信息

Institute for Biochemistry and Molecular Biology, University of Freiburg, Stefan-Meier-Str.17, 79104 Freiburg, Germany; BIOSS, Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.

出版信息

Biochem Biophys Res Commun. 2018 May 27;500(1):26-34. doi: 10.1016/j.bbrc.2017.06.190. Epub 2017 Jul 1.

DOI:10.1016/j.bbrc.2017.06.190

PMID:28676391

Abstract

Proteins of the B-cell lymphoma-2 (BCL-2) family control the intrinsic apoptosis pathway. The pro-apoptotic BCL-2 proteins BAX and BAK can commit a cell to its programmed death by permeabilizing the outer mitochondrial membrane (OMM) and subsequent initiation of the caspase cascade. Therefore, the activities of BAX and BAK are precisely controlled by a complex network of proteins inside and outside the BCL-2 family. Cells survive by constant control of dynamic translocation and retrotranslocation of BAX and BAK to the mitochondria and back into the cytosol. Recent insights into BAX/BAK shuttling, BCL-2 protein interactions, the role of BH3-only proteins in apoptosis signaling and the active BAX complex set the stage for the development of novel strategies in cancer therapy and the analysis of cellular predisposition to apoptosis.

摘要

BCL-2 家族蛋白控制着细胞的内在凋亡途径。促凋亡的 BCL-2 蛋白 BAX 和 BAK 可以通过使线粒体外膜（OMM）通透，进而启动半胱氨酸蛋白酶级联反应，使细胞走向程序性死亡。因此，BAX 和 BAK 的活性受到 BCL-2 家族内外的蛋白质组成的复杂网络的精细调控。通过对 BAX 和 BAK 在线粒体和细胞质之间的动态易位和反向易位的持续控制，细胞得以存活。最近对 BAX/BAK 穿梭、BCL-2 蛋白相互作用、BH3 仅有蛋白在凋亡信号中的作用以及活性 BAX 复合物的深入了解，为癌症治疗新策略的开发和细胞对凋亡的易感性分析奠定了基础。