Autoproteolytic activation of pro-caspases by oligomerization
Autoproteolytic activation of pro-caspases by oligomerization
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DOI：
10.1016/s1097-2765(00)80032-5
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发表时间：
1998-01-01
期刊：
影响因子：
16
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Yang, XL;Chang, HY;Baltimore, D
细胞凋亡的启动需要半胱天冬酶原转化为成熟的半胱天冬酶。在这里，我们表明半胱天冬酶原的寡聚足以诱导成熟半胱天冬酶亚基的蛋白水解生成并激活其细胞死亡活性。从 pro-caspase-8 中删除蛋白质相互作用基序 DED 会极大地抑制其凋亡活性。通过两个异源诱导性寡聚化系统对 caspase-8 蛋白酶原结构域进行寡聚化，可以恢复细胞死亡活性。诱导的寡聚化还会激活 caspase-1 前体的凋亡活性，但不会激活 caspase-3 前体的凋亡活性。在体外，寡聚化导致 caspase 前体加工形成成熟的 caspase 亚基；该过程需要酶原的内在半胱天冬酶活性，并通过新的裂解事件顺序进行。
Initiation of apoptosis requires the conversion of pro-caspases to mature caspases. Here we show that oligomerization of pro-caspases is sufficient to induce proteolytic generation of mature caspase subunits and activation of their cell death activity. Deletion of the protein interaction motif DED from pro-caspase-8 greatly suppresses its apoptotic activity. Cell death activity can be restored by oligomerization of pro-caspase-8 protease domains by two heterologous inducible oligomerization systems. Induced oligomerization also activates the apoptotic activity of pro-caspase-1 but not pro-caspase-3. In vitro, oligomerization leads to pro-caspase processing to form the mature caspase subunits; this processing requires the intrinsic caspase activity of zymogens and proceeds via a novel order of cleavage events.