Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
J Cell Biol. 2012 Feb 20;196(4):513-27. doi: 10.1083/jcb.201107133.
Essentially, all metazoan cells can undergo apoptosis, but some cells are more sensitive than others to apoptotic stimuli. To date, it is unclear what determines the apoptotic potential of the cell. We set up an in vivo system for monitoring and comparing the activity levels of the two main effector caspases in Drosophila melanogaster, Drice and Dcp-1. Both caspases were activated by the apoptosome after irradiation. However, whereas each caspase alone could induce apoptosis, Drice was a more effective inducer of apoptosis than Dcp-1, which instead had a role in establishing the rate of cell death. These functional differences are attributed to their intrinsic properties rather than merely their tissue specificities. Significantly, the levels of the procaspases are directly proportional to their activity levels and play a key role in determining the cell's sensitivity to apoptosis. Finally, we provide evidence for the existence of a cellular execution threshold of caspase activity, which must be reached to induce apoptosis.
本质上，所有后生动物细胞都可以经历细胞凋亡，但有些细胞对凋亡刺激比其他细胞更敏感。迄今为止，尚不清楚是什么决定了细胞的凋亡潜能。我们建立了一个体内系统来监测和比较黑腹果蝇中两种主要效应半胱天冬酶 Drice 和 Dcp-1 的活性水平。两种半胱天冬酶在照射后都被凋亡体激活。然而，虽然每种半胱天冬酶单独都可以诱导细胞凋亡，但 Drice 比 Dcp-1 更有效地诱导细胞凋亡，而 Dcp-1 在确定细胞死亡速度方面起作用。这些功能差异归因于它们的内在特性，而不仅仅是它们的组织特异性。重要的是，前半胱天冬酶的水平与它们的活性水平成正比，并在决定细胞对细胞凋亡的敏感性方面起着关键作用。最后，我们提供了证据证明细胞凋亡半胱天冬酶活性存在细胞执行阈值，必须达到该阈值才能诱导细胞凋亡。
