Venancio Thiago M, Balaji S, Iyer Lakshminarayan M, Aravind L
National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
Genome Biol. 2009;10(3):R33. doi: 10.1186/gb-2009-10-3-r33. Epub 2009 Mar 30.
The ubiquitin system (Ub-system) can be defined as the ensemble of components including Ub/ubiquitin-like proteins, their conjugation and deconjugation apparatus, binding partners and the proteasomal system. While several studies have concentrated on structure-function relationships and evolution of individual components of the Ub-system, a study of the system as a whole is largely lacking.
Using numerous genome-scale datasets, we assemble for the first time a comprehensive reconstruction of the budding yeast Ub-system, revealing static and dynamic properties. We devised two novel representations, the rank plot to understand the functional diversification of different components and the clique-specific point-wise mutual-information network to identify significant interactions in the Ub-system.
Using these representations, evidence is provided for the functional diversification of components such as SUMO-dependent Ub-ligases. We also identify novel components of SCF (Skp1-cullin-F-box)-dependent complexes, receptors in the ERAD (endoplasmic reticulum associated degradation) system and a key role for Sus1 in coordinating multiple Ub-related processes in chromatin dynamics. We present evidence for a major impact of the Ub-system on large parts of the proteome via its interaction with the transcription regulatory network. Furthermore, the dynamics of the Ub-network suggests that Ub and SUMO modifications might function cooperatively with transcription control in regulating cell-cycle-stage-specific complexes and in reinforcing periodicities in gene expression. Combined with evolutionary information, the structure of this network helps in understanding the lineage-specific expansion of SCF complexes with a potential role in pathogen response and the origin of the ERAD and ESCRT systems.
泛素系统（Ub 系统）可定义为包括 Ub/泛素样蛋白、其缀合和解缀合装置、结合伴侣以及蛋白酶体系统在内的一组组件。虽然已有多项研究聚焦于 Ub 系统单个组件的结构 - 功能关系及进化，但对整个系统的研究仍十分匮乏。
利用大量基因组规模数据集，我们首次对出芽酵母 Ub 系统进行了全面重构，揭示了其静态和动态特性。我们设计了两种新颖的表示方法，即用于理解不同组件功能多样化的秩图，以及用于识别 Ub 系统中显著相互作用的团簇特异性点向互信息网络。
利用这些表示方法，为 SUMO 依赖性 Ub 连接酶等组件的功能多样化提供了证据。我们还鉴定了 SCF（Skp1 - cullin - F - box）依赖性复合物的新组件、内质网相关降解（ERAD）系统中的受体以及 Sus1 在协调染色质动力学中多个 Ub 相关过程的关键作用。我们提供证据表明 Ub 系统通过与转录调控网络相互作用，对蛋白质组的大部分区域产生重大影响。此外，Ub 网络的动态变化表明 Ub 和 SUMO 修饰可能在调节细胞周期阶段特异性复合物以及增强基因表达的周期性方面与转录控制协同发挥作用。结合进化信息，该网络的结构有助于理解 SCF 复合物在病原体应答中的潜在作用以及 ERAD 和 ESCRT 系统起源方面的谱系特异性扩展。
