Molecular cloning and identification of murine caspase-8

Several caspases are mediators of apoptotic cell death. We describe a novel murine member of this growing protein family. Based on homology and especi ally on the substrate specificity, this new procaspase is identified as the murine counterpart of human procaspase-8. The protein exhibits a rather lo w similarity (76%) and identity (70%) to human procaspase-8. Procaspase-8 m RNA is expressed in all adult mouse tissues examined, the highest levels be ing reached in kidney, liver and lung. Procaspase-8 mRNA expression is high est in seven-day old embryos, but also during later stages of development t he expression was fairly high. Both human and murine procaspase-8 are very weak substrates for granzyme B as compared to procaspase-3. Murine procaspa ses-1, 2, 3, 6, 7, 8, 11/4 and 12 are processed by recombinant murine caspa se-8, suggesting a key role in the procaspase activation cascade. In additi on, murine caspase-8 induced cell death that was inhibited both by cytokine response modifier A and p35. In vitro experiments demonstrated that p35 in hibits caspase-8 directly. (C) 1998 Academic Press.