Apaf1 is required for mitochondrial pathways of apoptosis and brain development
Apaf1 is required for mitochondrial pathways of apoptosis and brain development
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DOI：
10.1016/s0092-8674(00)81733-x
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发表时间：
1998-09-18
期刊：
影响因子：
64.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Yoshida, H;Kong, YY;Mak, TW
细胞凋亡对于细胞稳态和发育的精确调节是必不可少的。Apaf 1是C. elegans CED-4在基因靶向Apaf 1（-/-）小鼠中进行了研究。apaf 1缺陷小鼠表现出减少脑细胞凋亡和显着颅面神经元细胞过度增殖异常。Apaf 1缺陷细胞对多种凋亡刺激具有抗性，并且半胱天冬酶2、3和8的加工受损。然而，Apaf 1（-/-）胸腺细胞和活化的T淋巴细胞对Fas诱导的杀伤敏感，表明Fas介导的这些细胞的凋亡是独立的Apaf 1。这些数据表明，Apaf 1在大多数死亡途径中的共同事件中起着核心作用，这种作用对正常发育至关重要。
Apoptosis is essential for the precise regulation of cellular homeostasis and development. The role in vivo of Apaf1, a mammalian homolog of C. elegans CED-4, was investigated in gene-targeted Apaf1(-/-) mice. Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1(-/-) thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.