Essential role of CED-4 oligomerization in CED-3 activation and apoptosis.
Essential role of CED-4 oligomerization in CED-3 activation and apoptosis.
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DOI：
10.1126/science.281.5381.1355
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发表时间：
1998-08
期刊：
影响因子：
56.9
通讯作者：
Xiaolu Yang;Howard Y. Chang;D. Baltimore
中科院分区：
文献类型：
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作者：
Xiaolu Yang;Howard Y. Chang;D. Baltimore
控制细胞凋亡的激活在发育和抗癌保护中都是重要的。在经典的遗传模型秀丽隐杆线虫中，促凋亡蛋白CED-4激活CED-3半胱天冬酶，并被Bcl-2样蛋白CED-9抑制。这两个过程都是由蛋白质-蛋白质相互作用介导的。发现促进CED-3酶原分子的接近诱导半胱天冬酶活化和细胞死亡。CED-4蛋白在细胞和体外寡聚化。这种寡聚化诱导CED-3接近并与CED-4：CED-9相互作用竞争。消除CED-4寡聚化的突变使其激活CED-3的能力失活。因此，控制机制是CED-3：CED-4复合物中的CED-3被CED-4寡聚化激活，而CED-4寡聚化被CED-9与CED-4的结合抑制。
Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2-like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.