The COP9 signalosome is essential for development of Drosophila melanogaster
The COP9 signalosome is essential for development of Drosophila melanogaster
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DOI：
10.1016/s0960-9822(00)80023-8
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发表时间：
1999-10-21
期刊：
影响因子：
9.2
通讯作者：
Chamovitz, DA
中科院分区：
文献类型：
--
作者：
Freilich, S;Oron, E;Chamovitz, DA
COP 9信号体（最初描述为COP 9复合物）是植物中光调节发育的重要多亚基阻遏物[1，2]，它也已在哺乳动物中被鉴定，尽管其作用仍然不清楚[3-5]。该复合物类似于蛋白酶体和eIF 3的调节盖[5，9 -12]，并且已知其几个亚基参与激酶信号传导途径[4，6 -8]，在酿酒酵母基因组中未鉴定出与COP 9信号体组分同源的蛋白，表明COP 9信号体对多细胞分化具有特异性[13]，为了揭示COP 9信号体在动物体内的发育功能，我们分离了果蝇COP 9信号体的8个亚基的基因，并通过免疫共沉淀和凝胶过滤分析表明，这些蛋白质是果蝇COP 9信号体的组成部分。酵母双杂交试验表明，这些蛋白质相互作用，一些通过PCI域。通过P-元件插入或基因缺失破坏其中一个亚基会导致幼虫或蛹晚期的致死性。这种致死性可能是多种多效性作用的结果。我们的研究结果表明，COP 9信号体在无脊椎动物中是保守的，它在动物发育中起着至关重要的作用。
The COP9 signalosome (originally described as the COP9 complex) is an essential multi-subunit repressor of light regulated development in plants [1,2], It has also been identified in mammals, though its role remains obscure [3-5]. This complex is similar to the regulatory lid of the proteasome and eIF3 [5,9-12] and several of its subunits are known to be involved in kinase signaling pathways [4,6-8], No proteins homologous to COP9 signalosome components were identified in the Saccharomyces cerevisiae genome, suggesting that the COP9 signalosome is specific for multi-cellular differentiation [13], In order to reveal the developmental function of the COP9 signalosome in animals, we have isolated Drosophila melanogaster genes encoding eight subunits of the COP9 signalosome, and have shown by co-immunoprecipitation and gel-filtration analysis that these proteins are components of the Drosophila COP9 signalosome. Yeast two-hybrid assays indicated that several of these proteins interact, some through the PCI domain. Disruption of one of the subunits by either a P-element insertion or deletion of the gene caused lethality at the late larval or pupal stages. This lethality is probably a result of numerous pleiotropic effects. Our results indicate that the COP9 signalosome is conserved in invertebrates and that it has an essential role in animal development.