Unique and overlapping substrate specificities of caspase-8 and caspase-10

被引:76
作者
Fischer, U [1 ]
Stroh, C [1 ]
Schulze-Osthoff, K [1 ]
机构
[1] Univ Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany
关键词
apoptosis; caspase-10; caspase-8; Bid; RIP;
D O I
10.1038/sj.onc.1209015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:152 / 159
页数:8
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