The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex
The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex
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DOI：
10.1016/s1097-2765(00)80456-6
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发表时间：
1999-03-01
期刊：
影响因子：
16
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Puthalakath, H;Huang, DCS;Strasser, A
BCL-2家族中只有一个BH3同源结构域的成员是强有力的细胞凋亡诱导者，其中一些似乎在发育中的程序性细胞死亡中起着关键作用。我们研究了BH3-Only蛋白RIM的促凋亡活性的调节。在健康细胞中，大多数Rim分子与LC8细胞质动力蛋白轻链结合，从而隔离到微管相关的动力蛋白运动复合体。某些细胞凋亡刺激干扰了LC8和动力蛋白运动复合体之间的相互作用。这释放了RIM，使其与LC8一起移位到Bcl-2上，并中和了其抗凋亡活性。这一过程不需要caspase活性，因此构成了细胞凋亡信号的启动事件。
Bcl-2 family members that have only a single Bcl-2 homology domain, BH3, are potent inducers of apoptosis, and some appear to play a critical role in developmentally programmed cell death. We examined the regulation of the proapoptotic activity of the BH3-only protein Rim. In healthy cells, most Rim molecules were bound to LC8 cytoplasmic dynein light chain and thereby sequestered to the microtubule-associated dynein motor complex. Certain apoptotic stimuli disrupted the interaction between LC8 and the dynein motor complex. This freed Rim to translocate together with LC8 to Bcl-2 and to neutralize its antiapoptotic activity. This process did not require caspase activity and therefore constitutes an initiating event in apoptosis signaling.