Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-related channel-independent apoptosis
Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-related channel-independent apoptosis
复制标题
DOI：
10.1074/jbc.m512610200
复制
发表时间：
2006-08-18
影响因子：
4.8
通讯作者：
Ogihara, Toshio
中科院分区：
文献类型：
--
作者：
Yasuda, Osamu;Fukuo, Keisuke;Ogihara, Toshio
在细胞凋亡的内在途径中，线粒体通过将细胞色素c从膜间隙释放到细胞质中而发挥关键作用。线粒体中细胞色素c通过Bax/Bak依赖性通道释放已被充分记录。相比之下，亲环素D（CypD），渗透性转换孔依赖性蛋白质释放的重要组成部分，仍然在很大程度上是不确定的，并没有特异性作用于CypD依赖性方式的促凋亡蛋白质已被报道。在这里，我们描述了一种新的和进化上保守的蛋白质，Apop。小鼠Apop-1表达通过将细胞色素c从线粒体释放到胞质空间中，随后激活半胱天冬酶-9和-3来诱导凋亡性死亡。Apop-1诱导的细胞凋亡不被Bax/Bak依赖性通道的抑制剂Bcl-2或Bcl-x（L）阻断，而它被渗透性转换孔的抑制剂环孢菌素A完全阻断。缺乏CypD的细胞对Apop诱导的凋亡具有抗性。此外，抑制Apop表达防止了由凋亡诱导物质诱导的细胞死亡。因此，我们的研究结果表明，Apop-1的表达通过CypD依赖性途径诱导细胞凋亡，并且Apop-1在生理条件下在细胞死亡中起作用。
In the intrinsic pathway of apoptosis, mitochondria play a crucial role by releasing cytochrome c from the intermembrane space into the cytoplasm. Cytochrome c release through Bax/Bak-dependent channels in mitochondria has been well documented. In contrast, cyclophilin D ( CypD), an important component of permeability transition pore-dependent protein release, remains largely undefined, and no apoptogenic proteins that act specifically in a CypD-dependent manner have been reported to date. Here, we describe a novel and evolutionarily conserved protein, apoptogenic protein ( Apop). Mouse Apop-1 expression induces apoptotic death by releasing cytochrome c from mitochondria into the cytosolic space followed by activation of caspase-9 and -3. Apop-1-induced apoptosis is not blocked by Bcl-2 or Bcl-x(L), inhibitors of Bax/Bak-dependent channels, whereas it is completely blocked by cyclosporin A, an inhibitor of permeability transition pore. Cells lacking CypD were resistant to Apop-induced apoptosis. Moreover, inhibition of Apop expression prevented the cell death induced by apoptosis-inducing substances. Our findings, thus, indicate that the expression of Apop-1 induces apoptosis though CypD-dependent pathway and that Apop-1 plays roles in cell death under physiological conditions.