The apoptotic initiator caspase-8: its functional ubiquity and genetic diversity during animal evolution.
The apoptotic initiator caspase-8: its functional ubiquity and genetic diversity during animal evolution.
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DOI：
10.1093/molbev/msu260
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发表时间：
2014-09
影响因子：
10.7
通讯作者：
K. Sakamaki;K. Shimizu;Hiroaki Iwata;K. Imai;Y. Satou;N. Funayama;M. Nozaki;Mamiko Yajima;Osamu Nishimura;Mayura Higuchi;K. Chiba;M. Yoshimoto;Haruna Kimura;A. Gracey;Takashi Shimizu;K. Tomii;O. Gotoh;K. Akasaka;T. Sawasaki;David J. Miller
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文献类型：
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作者：
K. Sakamaki;K. Shimizu;Hiroaki Iwata;K. Imai;Y. Satou;N. Funayama;M. Nozaki;Mamiko Yajima;Osamu Nishimura;Mayura Higuchi;K. Chiba;M. Yoshimoto;Haruna Kimura;A. Gracey;Takashi Shimizu;K. Tomii;O. Gotoh;K. Akasaka;T. Sawasaki;David J. Miller
半胱氨酸蛋白酶是半胱氨酸蛋白酶家族，在细胞凋亡、炎症和细胞分化中发挥多种作用。Caspase-8(Caspase-8)是最早在人类中发现的基因，在细胞表面死亡受体介导的细胞凋亡信号中起着启动子作用。为了了解Casp8蛋白家族的功能进化，从广泛的脊椎动物和无脊椎动物(包括海绵和脊椎动物)中鉴定了casp8同源基因，并在基因和蛋白质水平上进行了特征分析。一些内含子从爬行动物到哺乳动物都是保守的，但也发生了丢失和获得；在硬骨鱼进化过程中出现了一个新的内含子，而在海鞘动物中，casp8基因是无内含子的，并与邻近基因组织在一个操纵子中。Casp8活性在整个动物界几乎无处不在。在培养的哺乳动物细胞中外源表达一系列具有代表性的非哺乳动物Casp8蛋白可诱导细胞死亡，这意味着这些蛋白具有促凋亡活性。Casp8蛋白在催化口袋中的氨基酸残基方面与它们的双边对应蛋白有很大的不同，但表现出与人CASP8相同的底物特异性，突显了参与酶活性的空间结构相互作用的复杂性。最后，研究证实，与接头分子Fas相关的死亡结构域蛋白的相互作用在进化上也是古老的。因此，尽管结构的多样性和多种新功能的共同作用，这种活动的古老起源和几乎无处不在的分布在动物界强调了Casp8作为后生动物分子工具箱的中心组件的重要性和实用性。
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.