Unique and overlapping substrate specificities of caspase-8 and caspase-10
Unique and overlapping substrate specificities of caspase-8 and caspase-10
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DOI：
10.1038/sj.onc.1209015
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发表时间：
2006-01-01
期刊：
影响因子：
8
通讯作者：
Schulze-Osthoff, K
中科院分区：
文献类型：
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作者：
Fischer, U;Stroh, C;Schulze-Osthoff, K
虽然caspase-8作为死亡受体介导的细胞凋亡的启动者已经确定，但其最接近的同源物caspase-10的功能几乎完全未知。为了更深入地了解caspase-10的生理功能，我们比较了两种启动子caspase-8对已知caspase-8底物的切割情况。我们证明了caspase-10和-8对几种底物有重叠的切割偏好，如激酶RIP和PAK2。有趣的是，在其他底物中，如Bcl-2蛋白BID，我们发现了两个caspase额外和明显的切割位点，这可能对线粒体靶向和死亡信号的传播具有重要影响。Caspase-8和-10还导致其酶前体的不同链间裂解模式。综上所述，这些结果表明，尽管caspase-8和-10具有重叠的功能，但也具有选择性底物切割特异性，因此可能在细胞凋亡信号中发挥非多余的作用。
Although caspase-8 has an established role as an initiator of death receptor-mediated apoptosis, the function of its closest homolog, caspase-10, is almost completely unknown. To gain a closer insight into the physiological function of caspase-10, we compared the cleavage of known caspase-8 substrates by both initiator caspases. We demonstrate that caspase-10 and -8 have overlapping cleavage preferences for several substrates such as the kinases RIP and PAK2. Interestingly, in other substrates, such as the Bcl-2 protein Bid, we found additional and distinct cleavage sites for both caspases, which might have important consequences for mitochondrial targeting and propagation of the death signal. Caspase-8 and -10 also caused different interchain cleavage patterns of their enzyme precursors. Together, these results suggest that caspase-8 and -10, despite having overlapping functions, also have selective substrate cleavage specificities and might thereby exert nonredundant roles in apoptosis signaling.