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Building complex biological networks based upon model organisms: mapping the human autophagy interactome via a hybrid yeast-human protein interaction network.

机译:基于模型有机体构建复杂的生物网络:通过酵母-人蛋白质相互作用网络映射人自噬相互作用基因组。

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Autophagy is a process whose core machinery is highly conserved from yeast to higher eukaryotes and mammals. However it is becoming clear that multicellular organisms exhibit increased complexity of autophagic regulation and specialization of the non-core apparatus to perform a number of different roles. Using the yeast interaction network as a scaffold we identified 14 novel human gene products as putative autophagy-associated proteins. We confirmed one of these, the F-BAR protein FNBP1L, as being an ATG3 interactor. Using a functional siRNA approach we demonstrated that FNBP1L was essential for autophagy of internalized Salmonella typhimurium, but dispensable for formation of classical autophagosomes. Our approach illustrates the level of conservation of the autophagy apparatus over large evolutionary distances, but also demonstrates that mammalian cells utilize different autophagy accessory molecules in specific contexts.
机译:自噬是一个过程,其核心机制从酵母到高级真核生物和哺乳动物都高度保守。然而,越来越清楚的是,多细胞生物体表现出自噬调节的复杂性增加以及非核心装置的专门化以执行许多不同的作用。使用酵母相互作用网络作为支架,我们确定了14种新型人类基因产物作为推定的自噬相关蛋白。我们确认其中一个F-BAR蛋白FNBP1L是ATG3相互作用子。使用功能性siRNA方法,我们证明了FNBP1L对于内化鼠伤寒沙门氏菌的自噬是必不可少的,但对于形成经典自噬体却是必不可少的。我们的方法说明了自噬设备在较大进化距离上的保守水平,但也表明哺乳动物细胞在特定情况下利用了不同的自噬辅助分子。

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