Czabotar P E, Colman P M, Huang D C S
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
Cell Death Differ. 2009 Sep;16(9):1187-91. doi: 10.1038/cdd.2009.83. Epub 2009 Jun 26.
The mechanism by which the cell death mediator Bax becomes activated to cause mitochondrial damage, a key step for the intrinsic pathway to apoptosis, remain highly contentious. Although some data support a role for certain BH3-only proteins, such as Bim or tBid, to directly activate Bax, others have led to the conclusion that BH3-only proteins act indirectly by antagonizing the prosurvival Bcl-2 proteins, thereby allowing Bax activation to proceed. A recent paper in Nature by Gavathiotis et al. provides the first biophysical evidence for a direct interaction between a BH3 domain, that of Bim, with Bax. Here, we review these intriguing observations and discuss their implications for our understanding of how the BH3-only proteins initiate apoptosis.
细胞死亡介质Bax被激活从而导致线粒体损伤的机制，这是细胞内凋亡途径的关键步骤，仍然存在很大争议。尽管一些数据支持某些仅含BH3结构域的蛋白质（如Bim或tBid）直接激活Bax的作用，但其他研究得出的结论是，仅含BH3结构域的蛋白质通过拮抗促生存的Bcl-2蛋白间接发挥作用，从而使Bax激活得以进行。Gavathiotis等人近期发表在《自然》杂志上的一篇论文提供了首个生物物理学证据，证明Bim的BH3结构域与Bax之间存在直接相互作用。在此，我们回顾这些有趣的观察结果，并讨论它们对于我们理解仅含BH3结构域的蛋白质如何启动凋亡的意义。
