Yoshida H, Kong Y Y, Yoshida R, Elia A J, Hakem A, Hakem R, Penninger J M, Mak T W
The Amgen Institute, Department of Medical Biophysics, University of Toronto, Canada.
Cell. 1998 Sep 18;94(6):739-50. doi: 10.1016/s0092-8674(00)81733-x.
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.
细胞凋亡对于细胞内稳态和发育的精确调控至关重要。对线虫CED - 4的哺乳动物同源物Apaf1，在基因靶向的Apaf1 - / -小鼠中研究了其在体内的作用。Apaf1缺陷型小鼠大脑中的细胞凋亡减少，且出现明显的颅面异常，伴有神经元细胞过度增殖。Apaf1缺陷型细胞对多种凋亡刺激具有抗性，半胱天冬酶2、3和8的加工过程受损。然而，Apaf1 - / -胸腺细胞和活化的T淋巴细胞对Fas诱导的杀伤敏感，表明这些细胞中Fas介导的细胞凋亡独立于Apaf1。这些数据表明，Apaf1在大多数死亡途径中线粒体依赖性细胞凋亡的共同事件中起核心作用，且该作用对正常发育至关重要。
