The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling.
The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling.
复制标题
DOI：
10.1083/jcb.140.6.1485
复制
发表时间：
1998-03-23
期刊：
影响因子：
--
通讯作者：
Rosen A
中科院分区：
文献类型：
--
作者：
Mancini M;Nicholson DW;Roy S;Thornberry NA;Peterson EP;Casciola-Rosen LA;Rosen A
Caspase-3介导的蛋白水解是凋亡过程的关键因素。最近的研究已经证明了线粒体蛋白的核心作用（例如，Bcl-2和细胞色素c）在caspase-3的激活中，通过涉及几种蛋白质分子相互作用的过程。使用特异性识别caspase-3前体形式的抗体，我们证明caspase-3酶原在非凋亡细胞中具有线粒体和细胞质分布。线粒体caspase-3前体包含在膜间隙中。各种凋亡刺激物的递送伴随着线粒体半胱天冬酶-3前体染色的丧失和半胱天冬酶-3蛋白水解活性的出现。我们建议，线粒体亚群的caspase-3前体分子耦合到一个独特的子集的凋亡信号通路，Bcl-2敏感，并通过多种特异性蛋白质相互作用转导。
Caspase-3–mediated proteolysis is a critical element of the apoptotic process. Recent studies have demonstrated a central role for mitochondrial proteins (e.g., Bcl-2 and cytochrome c) in the activation of caspase-3, by a process that involves interaction of several protein molecules. Using antibodies that specifically recognize the precursor form of caspase-3, we demonstrate that the caspase-3 proenzyme has a mitochondrial and cytosolic distribution in nonapoptotic cells. The mitochondrial caspase-3 precursor is contained in the intermembrane space. Delivery of a variety of apoptotic stimuli is accompanied by loss of mitochondrial caspase-3 precursor staining and appearance of caspase-3 proteolytic activity. We propose that the mitochondrial subpopulation of caspase-3 precursor molecules is coupled to a distinct subset of apoptotic signaling pathways that are Bcl-2 sensitive and that are transduced through multiple mitochondrion-specific protein interactions.