RRC ID 28640
著者 Sakamaki K, Nozaki M, Kominami K, Satou Y.
タイトル The evolutionary conservation of the core components necessary for the extrinsic apoptotic signaling pathway, in Medaka fish.
ジャーナル BMC Genomics
Abstract BACKGROUND:Death receptors on the cell surface and the interacting cytosolic molecules, adaptors and initiator caspases, are essential as core components of the extrinsic apoptotic signaling pathway. While the apoptotic machinery governing the extrinsic signaling pathway is well characterized in mammals, it is not fully understood in fish.
RESULTS:We identified and characterized orthologs of mammalian Fas, FADD and caspase-8 that correspond to the death receptor, adaptor and initiator caspase, from the Medaka fish (Oryzias latipes). Medaka Fas, caspase-8 and FADD exhibited protein structures similar to that of their mammalian counterparts, containing a death domain (DD), a death effector domain (DED) or both. Functional analyses indicated that these molecules possess killing activity in mammalian cell lines upon overexpression or following activation by apoptotic stimuli, suggesting similar pro-apoptotic functions in the extrinsic pathway as those in mammals. Genomic sequence analysis revealed that the Medaka fas (tnfrsf6), fadd and caspase-8 (casp8) genes are organized in a similar genomic structure as the mammalian genes. Database search and phylogenetic analysis revealed that the fas gene, but not the fadd and casp8 genes, appear to be present only in vertebrates.
CONCLUSION:Our results indicate that the core components necessary for the extrinsic apoptotic pathway are evolutionarily conserved in function and structure across vertebrate species. Based on these results, we presume the mechanism of apoptosis induction via death receptors was evolutionarily established during the appearance of vertebrates.
巻・号 8
ページ 141
公開日 2007-6-1
DOI 10.1186/1471-2164-8-141
PII 1471-2164-8-141
PMID 17540041
PMC PMC1903365
MeSH Amino Acid Sequence Animals Apoptosis* Base Sequence Caspase 8 / chemistry Caspase 8 / genetics* Caspase 8 / metabolism Cells, Cultured DNA, Complementary Databases, Genetic Embryo, Mammalian Embryo, Nonmammalian Evolution, Molecular* Exons Expressed Sequence Tags Fas Ligand Protein / chemistry Fas Ligand Protein / genetics* Fas Ligand Protein / metabolism Fas-Associated Death Domain Protein / chemistry Fas-Associated Death Domain Protein / genetics* Fas-Associated Death Domain Protein / metabolism Fibroblasts / cytology Fibroblasts / metabolism Fluorescent Antibody Technique, Indirect Genome HeLa Cells Humans Immunohistochemistry Mice Molecular Sequence Data NIH 3T3 Cells Open Reading Frames Oryzias / genetics* Oryzias / metabolism Phylogeny Protein Structure, Tertiary Receptors, Death Domain / chemistry Receptors, Death Domain / genetics* Receptors, Death Domain / metabolism Sequence Analysis, DNA Sequence Homology, Amino Acid Signal Transduction
IF 3.594
引用数 23
WOS 分野 BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY
リソース情報
遺伝子材料 pCS111-XtFas (Xenopus Fas) (RDB08077) mtgd021e23 (Molgula tectiformis FADD) (RDB08080)
ツメガエル・イモリ
メダカ Medaka EST clones