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 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.
Van de Craen
M
M
Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, K. L. Ledeganckstraat 35, Ghent, B-9000, Belgium.
Van Loo
G
G
Declercq
W
W
Schotte
P
P
Van den brande
I
I
Mandruzzato
S
S
van der Bruggen
P
P
Fiers
W
W
Vandenabeele
P
P
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000494:pharmacology; D013379:Substrate Specificity; D014018:Tissue Distribution; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000494:pharmacology
D061945:Caspase Inhibitors; D017931:DNA Primers; D004792:Enzyme Precursors; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D015843:Serpins; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C074641:interleukin-1beta-converting enzyme inhibitor; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases