Abstract
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.
Copyright 1998 Academic Press.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology
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Base Sequence
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Caspase 8
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Caspase 9
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Caspase Inhibitors
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Caspases / genetics*
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Caspases / metabolism
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Cell Line
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Cloning, Molecular
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DNA Primers / genetics
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Enzyme Precursors / genetics
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Enzyme Precursors / metabolism
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Granzymes
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Humans
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In Vitro Techniques
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Inhibitor of Apoptosis Proteins
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Mice
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Molecular Sequence Data
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Serine Endopeptidases / metabolism
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Serpins / genetics
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Serpins / pharmacology
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Substrate Specificity
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Tissue Distribution
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Transfection
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Viral Proteins / genetics
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Viral Proteins / pharmacology
Substances
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Caspase Inhibitors
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DNA Primers
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Enzyme Precursors
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Inhibitor of Apoptosis Proteins
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RNA, Messenger
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Serpins
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Viral Proteins
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inhibitor of apoptosis, Nucleopolyhedrovirus
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interleukin-1beta-converting enzyme inhibitor
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GZMB protein, human
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Granzymes
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Gzmb protein, mouse
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Serine Endopeptidases
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CASP8 protein, human
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CASP9 protein, human
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases