Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.
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DOI：
10.1371/journal.ppat.0030003
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发表时间：
2007-01
期刊：
影响因子：
6.7
通讯作者：
Peeters, Nemo
中科院分区：
文献类型：
--
作者：
Angot, Aurelie;Vergunst, Annette;Genin, Stephane;Peeters, Nemo
泛蛋白特异性地、共价地添加到蛋白质中，称为泛蛋白化，是一种真核细胞特异性修饰，对许多细胞过程（例如细胞周期进程、转录调节和激素信号传导）至关重要。多聚泛素化是26 S蛋白酶体破坏标记蛋白质的信号，但根据多聚泛素链拓扑结构，它也可以导致新的蛋白质特性。泛素协调的蛋白质降解和修饰也被证明是宿主对病原体的免疫反应所必需的。许多动物和植物病原菌利用III型和/或IV型分泌系统将效应蛋白注入宿主细胞，在那里它们破坏宿主信号级联作为其感染策略的一部分。最近在确定效应子功能方面的进展告诉我们，玩弄宿主的泛素化系统似乎是细菌的一种通用策略。在这里，我们讨论了细菌如何利用这个系统来控制其效应器的行动的时间，通过编程降解，阻止特定的中间体在哺乳动物或植物先天免疫，或靶向宿主蛋白质降解通过模仿特定的泛素/蛋白酶体系统组件。除了分析已在文献中描述的效应器，我们筛选了公开可用的细菌基因组的泛素蛋白酶体系统亚基的模拟，并检测到几个新的推定效应器。我们对病原体和宿主的泛素蛋白酶体系统之间的密切相互作用的理解才刚刚开始。这一令人兴奋的研究领域将有助于更好地理解这种相互作用，也可能为真核生物的泛素化过程提供新的见解。
The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome to destroy earmarked proteins, but depending on the polyubiquitin chain topology, it can also result in new protein properties. Both ubiquitin-orchestrated protein degradation and modification have also been shown to be essential for the host's immune response to pathogens. Many animal and plant pathogenic bacteria utilize type III and/or type IV secretion systems to inject effector proteins into host cells, where they subvert host signaling cascades as part of their infection strategy. Recent progress in the determination of effector function has taught us that playing with the host's ubiquitination system seems a general tactic among bacteria. Here, we discuss how bacteria exploit this system to control the timing of their effectors' action by programming them for degradation, to block specific intermediates in mammalian or plant innate immunity, or to target host proteins for degradation by mimicking specific ubiquitin/proteasome system components. In addition to analyzing the effectors that have been described in the literature, we screened publicly available bacterial genomes for mimicry of ubiquitin proteasome system subunits and detected several new putative effectors. Our understanding of the intimate interplay between pathogens and their host's ubiquitin proteasome system is just beginning. This exciting research field will aid in better understanding this interplay, and may also provide new insights into eukaryotic ubiquitination processes.