title: dad-1, an endogenous programmed cell death suppressor in Caenorhabditis elegans and vertebrates.
abstract: Programmed cell death (apoptosis) is a normally occurring process used to eliminate unnecessary or potentially harmful cells in multicellular organisms. Recent studies demonstrate that the molecular control of this process is conserved phylogenetically in animals. The dad-1 gene, which encodes a novel 113 amino acid protein, was originally identified in a mutant hamster cell line (tsBN7) that undergoes apoptosis at restrictive temperature. We have identified a dad-1 homologue in Caenorhabditis elegans (Ce-dad-1) whose predicted product is > 60% identical to vertebrate DAD-1. A search of the sequence databases indicated that DAD-1-like proteins are also expressed in two plant species. Expression of either human dad-1 or Ce-dad-1 under control of a C.elegans heat-shock-inducible promoter resulted in a reduction in the number of programmed cell death corpses visible in C.elegans embryos. Extra surviving cells were present in these animals, indicating that both the human and C.elegans dad-1 genes can suppress developmentally programmed cell death. Ce-dad-1 was found to rescue mutant tsBN7 hamster cells from apoptotic death as efficiently as the vertebrate genes. These results suggest that dad-1, which is necessary for cell survival in a mammalian cell line, is sufficient to suppress some programmed cell death in C.elegans.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison 53706, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sugimoto
authors.forename: R R
authors.initials: RR
authors.lastname: Hozak
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: T
authors.initials: T
authors.lastname: Nishimoto
authors.forename: J H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002478:Cells, Cultured; D006224:Cricetinae; D017238:Genes, Helminth; D016153:Genes, Suppressor; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D010614:Pharynx / Q000166:cytology / Q000196:embryology; D012097:Repressor Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C096021:Dad-1 protein, C elegans; D012097:Repressor Proteins