Caspase knockouts: matters of life and death

Caspase knockouts: matters of life and death
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Caspase 敲除:生死攸关

DOI:
10.1038/sj.cdd.4400593
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发表时间:
1999
影响因子:
12.4
通讯作者:
R. Flavell
R. Flavell
中科院分区:
生物学1区
文献类型:
--
作者:
T. S. Zheng;S. Hunot;K. Kuida;R. Flavell

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细胞凋亡是一种看似违反直觉的生理细胞自杀行为,是通过一种进化上保守的死亡程序来完成的,该程序的核心是激活一组称为半胱天冬酶的细胞内半胱氨酸蛋白酶。现在已经清楚,细胞外和细胞内刺激都通过触发这些原本潜伏的蛋白酶的激活来诱导细胞凋亡,该过程最终导致半胱天冬酶介导的细胞内容物分解以及随后被邻近细胞的吸收。虽然许多优雅的体外研究已经证明了大多数(如果不是全部)细胞凋亡的执行需要半胱天冬酶活性,但单个半胱天冬酶在体内的精确贡献以及它们在功能上如何相互关联仍然知之甚少。幸运的是,通过基因靶向产生各种 caspase 缺陷小鼠,为明确检查这些 caspase 体内的生理功能提供了独特的机会之窗。随着 caspase 敲除的列表不断增加,我们认为是时候回顾一下我们从这些研究中学到的知识,了解单个 caspase 在介导细胞凋亡事件中的确切作用。我们还将对这一不断发展的半胱天冬酶领域的未来研究方向做出预测。
Apoptosis, the seemingly counter-intuitive act of physiological cell suicide, is accomplished by an evolutionarily conserved death program that is centered on the activation of a group of intracellular cysteine proteases known as caspases. It is now clear that both extra- and intra-cellular stimuli induce apoptosis by triggering the activation of these otherwise latent proteases in a process that culminates in caspase-mediated disintegration of cellular contents and their subsequent absorption by neighboring cells. While many elegant in vitro studies have demonstrated the requirement of caspase activities for the execution of most, if not all, apoptosis, the precise contribution of individual caspases in vivo and how they functionally relate to each other remain poorly elucidated. Fortunately, the generation of various caspase deficient mice through gene targeting has provided a unique window of opportunity to definitely examine the physiological function of these caspases in vivo. As the list of caspase knockouts grows, we considered it was time to review what we have been learned, from these studies about the exact role of individual caspases in mediating apoptotic events. We will also provide our prediction on the direction of future studies in this ever-growing field of caspases.
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发表时间: 1998-11-10
影响因子: 11.1
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