Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3.
The mammalian interleukin-1 beta-converting enzyme (ICE) has sequence similarity to the C. elegans cell death gene ced-3. We show here that overexpression of the murine ICE (mICE) gene or of the C. elegans ced-3 gene causes Rat-1 cells to undergo programmed cell death. Point mutations in a region homologous between mICE and CED-3 eliminate the ability of mICE and ced-3 to cause cell death. The cell death caused by mICE can be suppressed by overexpression of the crmA gene, a specific inhibitor of ICE, as well as by bcl-2, a mammalian oncogene that can act to prevent programmed cell death. Our results suggest that ICE may function during mammalian development to cause programmed cell death.
Miura
M
M
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129.
Zhu
H
H
Rotello
R
R
Hartwieg
E A
EA
Yuan
J
J
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020170:Caspase 1; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D014764:Viral Proteins
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D020170:Caspase 1; D008666:Metalloendopeptidases