Caspases: cellular demolition experts
Caspases: cellular demolition experts
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DOI：
10.1042/bst0290696
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发表时间：
2001-01-01
影响因子：
3.9
通讯作者：
Martin, SJ
中科院分区：
文献类型：
--
作者：
Creagh, EM;Martin, SJ
细胞凋亡是由半胱氨酸蛋白酶家族来协调的，半胱氨酸蛋白酶通过靶向一整套蛋白质进行有限的蛋白质分解来分解细胞。哺乳动物caspase家族有14个成员，其中一部分参与细胞凋亡，其余的可能参与促炎细胞因子的处理。顶端caspase激活事件通常由促进caspase聚集和促进caspase自身激活的接头分子启动。相反，远端的caspase激活事件由级联中较早激活的caspase控制。许多细胞应激通过破坏线粒体引起细胞凋亡，导致释放触发caspase激活和细胞死亡的因子[如细胞色素c和Smac(线粒体衍生的第二个caspase激活剂)/Diablo]。在这里，我们讨论了线粒体细胞色素c释放到细胞质时触发的caspase级联反应的层次性，以及该级联反应中特定caspase在靶向蛋白质降解中的作用。最后，将讨论caspase级联中的反馈放大环路和重要控制点。
Apoptosis is co-ordinated by a family of cysteine proteases, the caspases, that dismantle the cell by targeting a panoply of proteins for limited proteolysis. The mammalian caspase family contains 14 members, a subset of which participates in apoptosis, with the remainder likely to be involved in the processing of pro-inflammatory cytokines. Apical caspase activation events are typically initiated by adaptor molecules that promote caspase aggregation and facilitate caspase autoactivation. In contrast, distal caspase activation events are controlled by caspases activated earlier in the cascade. Many cellular stresses provoke apoptosis by damaging mitochondria which results in the release of factors [such as cytochrome c and SMAC (second mitochondrial-derived activator of caspase)/Diablo] that trigger caspase activation and cell death. Here, we discuss the hierarchical nature of the caspase cascade that is triggered upon the release of mitochondrial cytochrome c into the cytoplasm, and the role of specific caspases within this cascade in targeting proteins for degradation. Finally, feedback amplification loops and important control points within the caspase cascade will be discussed.