Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Mol Cell. 2012 May 25;46(4):387-97. doi: 10.1016/j.molcel.2012.04.026.
Members of the caspase family of cysteine proteases coordinate the morphological and biochemical events that typify apoptosis. However, neutralization of caspase activity in mammals fails to block death in response to most proapoptotic stimuli. This is because many cell death triggers provoke mitochondrial dysfunction upstream of caspase activation as a consequence of BAX/BAK channel opening. Although genetic or pharmacological inactivation of caspases fails to block cell death in most instances, it does convert the phenotype from apoptosis to necrosis. This has important implications for how the immune system responds to such cells, as necrotic cells provoke inflammation whereas apoptotic cells typically do not. Here, we propose an alternative perspective on apoptosis-associated caspase function by suggesting that these proteases are activated, not to kill, but to extinguish the proinflammatory properties of dying cells. This perspective unifies the mammalian caspase family as either positive or negative regulators of inflammation.
半胱氨酸蛋白酶家族的胱天蛋白酶成员协调典型凋亡的形态和生化事件。然而，在哺乳动物中中和半胱天冬酶活性并不能阻止大多数促凋亡刺激物引起的死亡。这是因为许多细胞死亡触发物作为 BAX/BAK 通道开放的结果，在上游引发线粒体功能障碍，从而激活半胱天冬酶。尽管在大多数情况下，基因或药理学失活半胱天冬酶不能阻止细胞死亡，但它确实将表型从凋亡转变为坏死。这对免疫系统如何对这些细胞做出反应有重要影响，因为坏死细胞会引发炎症，而凋亡细胞通常不会。在这里，我们通过提出这些蛋白酶被激活不是为了杀死，而是为了消除垂死细胞的促炎特性，提出了一种与凋亡相关的半胱天冬酶功能的替代观点。这种观点将哺乳动物半胱天冬酶家族统一为炎症的正或负调节剂。
