Molecular cloning and identification of murine caspase-8

被引:30
作者
Van de Craen, M
Van Loo, G
Declercq, W
Schotte, P
Van den brande, I
Mandruzzato, S
van der Bruggen, P
Fiers, W
Vandenabeele, P [1 ]
机构
[1] Flanders Interuniv Inst Biotechnol, Dept Mol Biol, Ghent, Belgium
[2] State Univ Ghent, B-9000 Ghent, Belgium
[3] Catholic Univ Louvain, Ludwig Inst Canc Res, B-1200 Brussels, Belgium
[4] Catholic Univ Louvain, Unite Genet Cellulaire, B-1200 Brussels, Belgium
关键词
apoptosis; caspase-8; FLICE; granzyme B; p35;
D O I
10.1006/jmbi.1998.2226
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
Several caspases are mediators of apoptotic cell death. We describe a novel murine member of this growing protein family. Based on homology and especially on the substrate specificity, this new procaspase is identified as the murine counterpart of human procaspase-8. The protein exhibits a rather low similarity (76%) and identity (70%) to human procaspase-8. Procaspase-8 mRNA is expressed in all adult mouse tissues examined, the highest levels being reached in kidney, liver and lung. Procaspase-8 mRNA expression is highest in seven-day old embryos, but also during later stages of development the expression was fairly high. Both human and murine procaspase-8 are very weak substrates for granzyme B as compared to procaspase-3. Murine procaspases-1, 2, 3, 6, 7, 8, 11/4 and 12 are processed by recombinant murine caspase-8, suggesting a key role in the procaspase activation cascade. In addition, murine caspase-8 induced cell death that was inhibited both by cytokine response modifier A and p35. In vitro experiments demonstrated that p35 inhibits caspase-8 directly. (C) 1998 Academic Press.
引用
收藏
页码:1017 / 1026
页数:10
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