RRC ID 31335
著者 Sakamaki K, Shimizu K, Iwata H, Imai K, Satou Y, Funayama N, Nozaki M, Yajima M, Nishimura O, Higuchi M, Chiba K, Yoshimoto M, Kimura H, Gracey AY, Shimizu T, Tomii K, Gotoh O, Akasaka K, Sawasaki T, Miller DJ.
タイトル The apoptotic initiator caspase-8: its functional ubiquity and genetic diversity during animal evolution.
ジャーナル Mol. Biol. Evol.
Abstract The caspases, a family of cysteine proteases, play multiple roles in apoptosis, inflammation, and cellular differentiation. Caspase-8 (Casp8), which was first identified in humans, functions as an initiator caspase in the apoptotic signaling mediated by cell-surface death receptors. To understand the evolution of function in the Casp8 protein family, casp8 orthologs were identified from a comprehensive range of vertebrates and invertebrates, including sponges and cnidarians, and characterized at both the gene and protein levels. Some introns have been conserved from cnidarians to mammals, but both losses and gains have also occurred; a new intron arose during teleost evolution, whereas in the ascidian Ciona intestinalis, the casp8 gene is intronless and is organized in an operon with a neighboring gene. Casp8 activities are near ubiquitous throughout the animal kingdom. Exogenous expression of a representative range of nonmammalian Casp8 proteins in cultured mammalian cells induced cell death, implying that these proteins possess proapoptotic activity. The cnidarian Casp8 proteins differ considerably from their bilaterian counterparts in terms of amino acid residues in the catalytic pocket, but display the same substrate specificity as human CASP8, highlighting the complexity of spatial structural interactions involved in enzymatic activity. Finally, it was confirmed that the interaction with an adaptor molecule, Fas-associated death domain protein, is also evolutionarily ancient. Thus, despite structural diversity and cooption to a variety of new functions, the ancient origins and near ubiquitous distribution of this activity across the animal kingdom emphasize the importance and utility of Casp8 as a central component of the metazoan molecular toolkit.
巻・号 31(12)
ページ 3282-301
公開日 2014-9-11
DOI 10.1093/molbev/msu260
PII msu260
PMID 25205508
MeSH Amino Acid Sequence Animals Annelida / genetics Anthozoa / genetics Apoptosis* Base Sequence Caspase 8 / chemistry Caspase 8 / genetics* Ciona intestinalis / genetics Evolution, Molecular Fish Proteins / genetics Fishes / genetics HeLa Cells Humans Molecular Sequence Data Mytilus / genetics Phylogeny Planarians / genetics Protein Conformation Substrate Specificity
IF 6.202
引用数 6
WOS 分野 GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY EVOLUTIONARY BIOLOGY
リソース情報
カタユウレイボヤ・(ニッポンウミシダ) Wild C. int