Functional activation of Nedd2/ICH-1 (Caspase-2) is an early process in apoptosis
Functional activation of Nedd2/ICH-1 (Caspase-2) is an early process in apoptosis
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DOI：
10.1074/jbc.272.20.13134
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发表时间：
1997-05-16
影响因子：
4.8
通讯作者：
Kumar, S
中科院分区：
文献类型：
--
作者：
Harvey, NL;Butt, AJ;Kumar, S
ICE/CED-3 蛋白酶家族（半胱天冬酶）在细胞凋亡的执行阶段发挥着核心作用。这些蛋白酶被合成为前体分子，需要在特定的天冬氨酸残基处进行加工，以产生包含活性酶的两个亚基。已证明其中一些蛋白酶的激活发生在细胞凋亡过程中。在这里，我们表明 Nedd2/ICH-1 (caspase-2) 在各种凋亡刺激诱导的细胞凋亡过程中被激活，这种激活在用凋亡剂处理细胞时很早就发生，并且似乎先于 CPP32 (caspase-3) 的激活。在抗凋亡的细胞中未观察到 Nedd2 的激活。这些观察结果表明 Nedd2 是导致细胞死亡的途径中的早期效应子。我们的观察结果也证实了这样的假设：一组含有长前结构域的半胱天冬酶是最先响应细胞凋亡信号而被激活的，并且它们位于第二类半胱天冬酶（例如含有短前结构域或不含前结构域的 CPP32）的上游。
The ICE/CED-3 family of proteases (caspases) play a central role in the execution phase of apoptosis, These proteases are synthesised as precursor molecules that require processing at specific aspartate residues to pro duce the two subunits that comprise the active enzyme. The activation of some of these proteases has been shown to occur during apoptosis. Here we show that Nedd2/ICH-1 (caspase-2) is activated during apoptosis induced by a variety of apoptotic stimuli, This activation occurs very early upon treatment of cells with apoptotic agents and appears to precede the activation of CPP32 (caspase-3). The activation of Nedd2 was not seen in cells that are resistant to apoptosis, These observations suggest that Nedd2 is an early effector in the pathway leading to cell death. Our observations also lend weight to the hypothesis that a group of caspases containing long prodomains are the first to be activated in response to apoptotic signals and that they lie upstream of a second class of caspases such as CPP32 containing short or no prodomains.