title: Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death.
abstract: We report here the isolation and characterization of Ich-1, a gene related to the C. elegans cell death gene ced-3 and the mammalian homolog of ced-3, interleukin-1 beta-converting enzyme (ICE). Alternative splicing results in two distinct Ich-1 mRNA species. One mRNA species encodes a protein product of 435 amino acids (ICH-1L) that is homologous to both the P20 and P10 subunits of ICE (27% identity) and the entire CED-3 protein (28% identity). The other mRNA encodes a 312 amino acid truncated version of ICH-1L protein (ICH-1S). Overexpression of IchL induces programmed cell death, suggesting that Ich-1 is also a mammalian programmed cell death gene. More interestingly, overexpression of the Ich-1S suppresses Rat-1 cell death induced by serum deprivation. These observations suggest that Ich-1 plays an important role in both positive and negative regulation of programmed cell death in vertebrate animals.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital-East Charlestown 02129.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: L
authors.initials: L
authors.lastname: Bergeron
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Yuan
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D020170:Caspase 1; D053143:Caspase 2; D020169:Caspases; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000235:genetics; D006367:HeLa Cells; D015801:Helminth Proteins / Q000235:genetics*; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053143:Caspase 2; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; D020170:Caspase 1; D008666:Metalloendopeptidases