A human protein-protein interaction network:: A resource for annotating the proteome
A human protein-protein interaction network:: A resource for annotating the proteome
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DOI：
10.1016/j.cell.2005.08.029
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发表时间：
2005-09-23
期刊：
影响因子：
64.5
通讯作者：
Wanker, EE
中科院分区：
文献类型：
--
作者：
Stelzl, U;Worm, U;Wanker, EE
蛋白质相互作用图谱为更好地理解蛋白质组的功能组织提供了一个有价值的框架。为了系统地检测人类蛋白质的相互作用对，通过自动酵母双杂交（Y2 H）相互作用交配筛选4456个诱饵和5632个猎物的蛋白质基质。我们在1705个蛋白质中鉴定了3186个主要是新的相互作用，从而形成了一个大型的高度连接的网络。独立的下拉和免疫共沉淀试验验证了Y2 H相互作用的整体质量。使用拓扑学和GO标准，开发了一个评分系统，以定义401个蛋白质之间的911个高置信度相互作用。此外，该网络还搜索了将未表征的基因产物和人类疾病蛋白质与调节细胞途径联系起来的相互作用。实验验证了两种新的Axin-1相互作用，将ANP 32A和CRMP 1表征为Writ信号传导的调节剂。系统的人类蛋白质相互作用筛选可以更全面地了解蛋白质功能和细胞过程。
Protein-protein interaction maps provide a valuable framework for a better understanding of the functional organization of the proteome. To detect interacting pairs of human proteins systematically, a protein matrix of 4456 baits and 5632 preys was screened by automated yeast two-hybrid (Y2H) interaction mating. We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. Independent pull-down and coimmunoprecipitation assays validated the overall quality of the Y2H interactions. Using topological and GO criteria, a scoring system was developed to define 911 high-confidence interactions among 401 proteins. Furthermore, the network was searched for interactions linking uncharacterized gene products and human disease proteins to regulatory cellular pathways. Two novel Axin-1 interactions were validated experimentally, characterizing ANP32A and CRMP1 as modulators of Writ signaling. Systematic human protein interaction screens can lead to a more comprehensive understanding of protein function and cellular processes.